Publications by authors named "Celine Gys"

17 Publications

  • Page 1 of 1

Identification of chemicals of emerging concern in urine of Flemish adolescents using a new suspect screening workflow for LC-QTOF-MS.

Chemosphere 2021 Oct 27;280:130683. Epub 2021 Apr 27.

Toxicological Center, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium. Electronic address:

An essential step in human biomonitoring or molecular epidemiology programs is to estimate human exposure to environmental chemicals. Despite significant progress in the capabilities of analytical methods, the number of pollutants and their metabolites keeps increasing continuously. Some of these relatively unknown chemicals of emerging concern (CECs) may pose significant health risks to humans and biota, but remain virtually undetected in traditional HBM-studies. Non-target and suspect screening techniques based on high-resolution mass spectrometry (HRMS) perform the detection and identification of compounds without any a priori compound selection or chemical information and provide a more holistic overview of human exposure. In this study, 50 urine samples (25 female and 25 male) from a larger cohort of the Flemish Environment and Health Study (FLEHS IV, 2016-2020) have been submitted to suspect screening analysis, with the aim of detecting and identifying new CECs. For this purpose, an analytical method has been developed, optimised and evaluated in terms of analytical performance. Satisfactory results were obtained in terms of reproducibility, sensitivity and quality control. Data-mining was performed through the combination of two different workflows. The use of two complementary workflows enhanced the number of identified compounds. As a result, 45 CECs have been identified with a level of confidence ranged between 3 and 1. Most of the identified compounds were metabolisation products, many of which were currently not included in the targeted measurements of FLEHS IV. The identified chemicals and metabolites could be used as candidate biomarkers of exposure in future studies. Overall, the newly developed suspect screening workflow of this pilot study provided complementary and promising results for future HBM-programs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2021.130683DOI Listing
October 2021

Biomarkers of phthalates and alternative plasticizers in the Flemish Environment and Health Study (FLEHS IV): Time trends and exposure assessment.

Environ Pollut 2021 May 11;276:116724. Epub 2021 Feb 11.

Toxicological Center, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium. Electronic address:

Restrictions on the use of legacy phthalate esters (PEs) as plasticizer chemicals in several consumer products has led to the increased use of alternative plasticizers (APs), such as di-(iso-nonyl)-cyclohexane-1,2-dicarboxylate (DINCH) and di-(2-ethylhexyl) terephthalate (DEHTP). In the fourth cycle of the Flemish Environment and Health Study (FLEHS IV, 2016-2020), we monitored exposure to seven PEs (diethyl phthalate (DEP), di-(2-ethylhexyl) phthalate (DEHP), di-isobutyl phthalate (DiBP), di-n-butyl phthalate (DnBP), butylbenzyl phthalate (BBzP, di-isononyl phthalate (DINP), and di-isodecyl phthalate (DIDP))and three APs (DINCH, DEHTP, and di-(2-ethylhexyl) adipate (DEHA)) by measuring multiple biomarkers in urine of 416 adolescents from Flanders, Belgium (14-15 years old). The reference values show that exposure to PEs is still widespread, although levels of several PE metabolites (e.g., sum of DEHP metabolites, mono-normal-butyl phthalate (MnBP) and mono-benzyl phthalate (MBzP)) have decreased significantly compared to previous human biomonitoring cycles (2003-2018). On the other hand, metabolites of DINCH and DEHTP were detected in practically every participant. Concentrations of AP exposure biomarkers in urine were generally lower than PE metabolites, but calculations of estimated daily intakes (EDIs) showed that exposure to DINCH and DEHTP can be considerable. However, preliminary risk assessment showed that none of the EDI or urinary exposure levels of APs exceeded the available health-based guidance values, while a very low number of participants had levels of MiBP and MnBP exceeding the HBM value. Several significant determinants of exposure could be identified from multiple regression models: the presence of building materials containing PVC, ventilation habits, socio-economic status and season were all associated with PE and AP biomarker levels. Cumulatively, the results of FLEHS IV show that adolescents in Flanders, Belgium, are exposed to a wide range of plasticizer chemicals. Close monitoring over the last decade showed that the exposure levels of restricted PEs have decreased, while newer APs are now frequently detected in humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2021.116724DOI Listing
May 2021

Exposure levels, determinants and risk assessment of organophosphate flame retardants and plasticizers in adolescents (14-15 years) from the Flemish Environment and Health Study.

Environ Int 2021 02 6;147:106368. Epub 2021 Jan 6.

Toxicological Center, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium. Electronic address:

The ubiquitous use of organophosphate flame retardants and plasticizers (PFRs) in a variety of consumer products has led to widespread human exposure. Since certain PFRs are developmental and carcinogenic toxicants, detailed exposure assessments are essential to investigate the risk associated with environmental exposure levels. However, such data are still lacking for European countries. In this study, concentrations of thirteen PFR metabolites were measured in urine samples from 600 adolescents from Flanders, Belgium. 1-Hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP), diphenyl phosphate (DPHP), bis(1,3-dichloro-isopropyl) phosphate (BDCIPP), 2-hydroxyethyl bis(2-butoxyethyl) phosphate (BBOEHEP), 2-ethylhexyl phenyl phosphate (EHPHP) and 2-ethyl-5-hydroxyhexyl diphenyl phosphate (5-HO-EHDPHP) were frequently detected (>83%) in all participants. Comparisons with study populations from outside the EU showed that urinary levels of DPHP, BDCIPP and BCIPHIPP were generally within the same range. Only exposure to 2-ethylhexyl diphenyl phosphate (EHDPHP) was presumably higher in Flemish adolescents. However, determinants analysis through multivariate regression analyses did not reveal significant predictors that may explain this finding. Significantly higher levels of BDCIPP were observed in participants with new decorations at home, while adolescents with highly educated parents had higher levels of BBOEHEP and BDCIPP. Furthermore, multiple PFR metabolite concentrations followed a seasonal pattern. Estimated daily intakes (EDIs) were calculated from the internal dose by including fractions of urinary excretion (F) estimated in in vitro metabolism studies. EDIs ranged from 6.3 ng/kg bw/day for TBOEP to 567.7 ng/kg bw/day for EHDPHP, which were well below the available oral reference doses for all investigated PFRs. This suggests that the associated risk is low at present. This is the first report on internal exposure to seven commonly used PFRs in a European population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envint.2020.106368DOI Listing
February 2021

Determinants of exposure levels of bisphenols in flemish adolescents.

Environ Res 2021 02 1;193:110567. Epub 2020 Dec 1.

Toxicological Center, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium. Electronic address:

The broadly used industrial chemical bisphenol A (BPA), applied in numerous consumer products, has been under scrutiny in the past 20 years due to its widespread detection in humans and the environment and potential detrimental effects on human health. Following implemented restrictions and phase-out initiatives, BPA is replaced by alternative bisphenols, which have not received the same amount of research attention. As a part of the fourth cycle of the Flemish Environment and Health Study (FLEHS IV, 2016-2020), we monitored the internal exposure to six bisphenols in urine samples of 423 adolescents (14-15 years old) from Flanders, Belgium. All measured bisphenols were detected in the study population, with BPA and its alternatives bisphenol F (BPF) and bisphenol S (BPS) showing detection frequencies > 50%. The reference values show that exposure to these compounds is extensive. However, the urinary BPA level decreased significantly in Flemish adolescents compared to a previous cycle of the FLEHS (2008-2009). This suggests that the replacement of BPA with its analogues is ongoing. Concentrations of bisphenols measured in the Flemish adolescents were generally in the same order of magnitude compared to recent studies worldwide. Multiple regression models were used to identify determinants of exposure based on information on demographic and lifestyle characteristics of participants, acquired through questionnaires. Some significant determinants could be identified: sex, season, smoking behavior, educational level of the parents, recent consumption of certain foods and use of certain products were found to be significantly associated with levels of bisphenols. Preliminary risk assessment showed that none of the estimated daily intakes (EDIs) of BPA exceeded the tolerable daily intake, even in a high exposure scenario. For alternative bisphenols, no health-based guidance values are available, but in line with the measured urinary levels, their EDIs were lower than that of BPA. This study is, to the best of our knowledge, the first to determine internal exposure levels of other bisphenols than BPA in a European adolescent population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envres.2020.110567DOI Listing
February 2021

Short-term temporal variability of urinary biomarkers of organophosphate flame retardants and plasticizers.

Environ Int 2021 01 1;146:106147. Epub 2020 Nov 1.

Toxicological Center, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium. Electronic address:

Background: Exposure to organophosphate flame retardants and plasticizers (PFRs) is commonly estimated by measuring biomarker concentrations in spot urine samples. However, their concentrations in urine can vary greatly over time due to short biological half-lives and variable exposure, potentially leading to exposure misclassification. In this study, we examined the within- and between-individual and within- and between-day variability of PFR metabolites in spot and 24-hour pooled urine samples during five consecutive days.

Methods: We collected all spot urine samples from 10 healthy adults for 5 days. On one additional day, we collected 24-hour pooled urine samples. Samples were analyzed by solid-phase extraction coupled to high-performance liquid chromatography tandem mass spectrometry. We calculated intraclass correlation coefficients (ICCs) to assess the reproducibility of metabolite concentrations in morning void and spot samples.

Results: Fair-to-good reproducibility was observed for serial measurements of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP), 2-hydroxyethyl bis(2-butoxyethyl) phosphate (BBOEHEP) and 2-ethyl-5-hydroxyhexyl diphenyl phosphate (5-HO-EHDPHP) (ICC: 0.396 - 0.599), whereas concentrations of diphenyl phosphate (DPHP) and 2-ethylhexyl phenyl phosphate (EHPHP) were more variable in time (ICC: 0.303 and 0.234). Reproducibility improved significantly when only morning void samples were considered and when concentrations were adjusted for urinary dilution. Collecting 24-hour pooled urine could be a reliable alternative for PFR biomarkers with poor short-term temporal variability.

Conclusions: The between-day variability was minor compared to variability observed within the same day, which suggests that collecting multiple samples could reduce exposure missclassification. Differences in the observed between- and within-individual variance were compound specific and related to both the nature of the exposure (e.g., diet vs other exposure routes, multiple sources) and the individual toxicokinetic properties of the investigated PFRs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envint.2020.106147DOI Listing
January 2021

Kinetics and biotransformation products of bisphenol F and S during aerobic degradation with activated sludge.

J Hazard Mater 2021 02 24;404(Pt A):124079. Epub 2020 Sep 24.

Jožef Stefan Institute, Jamova cesta 39, 1000 Ljubljana, Slovenia; International Postgraduate School Jožef Stefan, Jamova cesta 39, 1000 Ljubljana, Slovenia. Electronic address:

Bisphenol F (BPF) and bisphenol S (BPS) are becoming widespread in the environment despite the lack of information regarding their fate during wastewater treatment and in the environment. This study assessed the biodegradation kinetics of BPF and BPS during biological wastewater treatment with activated sludge using GC-MS/MS, and the identification of biotransformation products (BTPs) using LC-QTOF-MS. The results showed that BPF and BPS degrade readily and unlikely accumulate in biosolids or wastewater effluent (c = 0.1 mg L, half-lives <4.3 days). The first-order kinetic model revealed that BPF (k = 0.20-0.38) degraded faster than BPS (k = 0.04-0.16) and that degradation rate decreases with an increasing initial concentration of BPS (half-lives 17.3 days). The absence of any additional organic carbon source significantly slowed down degradation, in particular, that of BPS (lag phase on day 18 instead of day 7). The machine-learning algorithm adopted as part of the non-targeted workflow identified three known BTPs and one novel BTP of BPF, and one known and ten new BTPs of BPS. The data from this study support possible new biodegradation pathways, namely sulphation, methylation, cleavage and the coupling of smaller bisphenol moieties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhazmat.2020.124079DOI Listing
February 2021

Short-term variability of bisphenols in spot, morning void and 24-hour urine samples.

Environ Pollut 2021 Jan 28;268(Pt A):115747. Epub 2020 Sep 28.

Toxicological Centre, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium. Electronic address:

Due to worldwide regulations on the application of the high production volume industrial chemical bisphenol A (BPA) in various consumer products, alternative bisphenols such as bisphenol F (BPF) and bisphenol S (BPS) are increasingly used. To assess human exposure to these chemicals, biomonitoring of urinary concentrations is frequently used. However, the short-term variability of alternative bisphenols has not been evaluated thoroughly yet, which is essential to achieve a correct estimation of exposure. In this study, we collected all spot urine samples from ten healthy adults for five consecutive days, and an additional 24 h pooled sample. We measured the concentrations of seven bisphenols (BPAF, BPF, BPA, BPB, BPZ, BPS and BPAP) in these samples using gas chromatography coupled to tandem mass spectrometry. BPA, BPF and BPS were frequently found in spot samples (>80%), while bisphenol AP (BPAP) was detected in 43% of spot samples. Calculations of intra-class correlation coefficients (ICCs) showed that reproducibility of these four bisphenols was relatively poor (<0.01-0.200) but improved when concentrations were corrected for urine dilution using creatinine levels (0.128-0.401). Of these four bisphenols, BPF showed the best reproducibility (ICC 0.200-0.439) and BPS the most variability (ICC <0.01-0.128). In general, the within-participant variability of bisphenol levels was the largest contributor to the total variance (47-100%). We compared repeated first morning voids to 24 h pooled urine and found no significantly different concentrations for BPA, BPF, BPS, or BPAP. Levels of BPA and BPF differed significantly depending on the sampling time throughout the day. The findings in this study suggest that collecting multiple samples per participant over a few days, in predefined time windows throughout the day, could result in a more reliable estimation of internal exposure to bisphenols.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2020.115747DOI Listing
January 2021

Between- and within-individual variability of urinary phthalate and alternative plasticizer metabolites in spot, morning void and 24-h pooled urine samples.

Environ Res 2020 12 24;191:110248. Epub 2020 Sep 24.

Toxicological Center, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium. Electronic address:

Due to international regulations, commonly used phthalates such as di(2-ethylhexyl) phthalate (DEHP) are being replaced by other phthalates, such as di-isononyl phthalate (DINP), and di-isodecyl phthalate (DIDP) and by alternative plasticizers (APs) with similar chemical characteristics, like di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH), di(2-ethylhexyl) terephthalate (DEHTP), or di-(2-ethylhexyl) adipate (DEHA). Urinary concentrations of metabolites are frequently used in the exposure assessment of non-persistent chemicals and for biomonitoring purposes, the intra- and inter-day variability of the metabolites should be known. However, the short-term variability of AP and several phthalate biomarkers has not been investigated yet. In this study, we collected all spot samples from 10 healthy adults for 5 consecutive days and 24h pooled urine on one additional day to investigate the short-term variability of 22 biomarkers of phthalates and APs. Metabolites of DEP, DEHP, DiBP, DnBP, DBzP, DINP and DIDP were found in high detection frequencies, while metabolites of most APs were found in approximately 50% of the samples. The short-term reproducibility of metabolites with diet as primary source (DEHP, DINP, DIDP) was poor (intraclass correlation coefficient - ICC < 0.4), whereas biomarkers of DEP, DnBP, DiBP and BBzP showed good consistency, most likely due to more continuous sources resulting in less between-day variance. ICC values of AP metabolites were similar to those of DEHP, but more studies are required to confirm these findings. Overall, reproducibility improved considerably when values were corrected for urinary dilution and when only morning voids samples were considered. Levels in morning voids samples were consistent for 5 days and comparable to 24-h pooled urine for all metabolites except for OH-MEHTP, sum DINP and sum DIDP, which supports the use of morning voids in human biomonitoring studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envres.2020.110248DOI Listing
December 2020

Biomonitoring and temporal trends of bisphenols exposure in Japanese school children.

Environ Res 2020 12 11;191:110172. Epub 2020 Sep 11.

Toxicological Centre, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium. Electronic address:

The widely used chemical bisphenol A (BPA), applied in various consumer products, has been under scrutiny in the past 20 years due to its widespread detection in humans and potential detrimental effects on human health. Following the implementation of restrictions and phase-out initiatives, BPA has been replaced by other structurally similar bisphenols, which have not yet received the same level of research attention. In this study, we aimed to 1) investigated the internal exposure to seven bisphenols in morning void urine samples (n = 396) from 7-year-old children from Hokkaido, Japan and 2) assess possible time trends in the concentrations of bisphenols between 2012 and 2017. Information on demographic, indoor environment and dietary characteristics of participants were acquired through a self-administered questionnaire. All bisphenols were detected in the study population, with BPA, BPF and BPS showing detection frequencies >50%. Concentrations of bisphenols measured in the Japanese children in our study were generally lower compared to studies worldwide. We found that BPA concentrations decreased significantly over the study time period (average 6.5% per year), whereas BPS rose with 2.8% per year. Levels of BPA and BPF were higher in autumn compared to winter. Higher urinary BPF levels were significantly associated with higher concentrations of the oxidative stress biomarker, 8-hydroxy-2'-deoxyguanosine (8-OHdG). BPA and BPF levels were higher in children from families with lower household income. Bisphenol concentrations were significantly influenced by some other personal (e.g. household income), food intake (e.g. vegetables and cow milk) and indoor housing characteristics (e.g. flooring). This is the first study to report longitudinal time trends of bisphenols in Japan. The presented findings imply that further research on bisphenols is warranted in the future to monitor whether these time trends continue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envres.2020.110172DOI Listing
December 2020

Exposure to organophosphate esters, phthalates, and alternative plasticizers in association with uterine fibroids.

Environ Res 2020 10 9;189:109874. Epub 2020 Jul 9.

School of Public Health, Seoul National University, Seoul, Republic of Korea. Electronic address:

Exposure to endocrine disrupting chemicals is suggested to be responsible for the development or progression of uterine fibroids. However, little is known about risks related to emerging chemicals, such as organophosphate esters (OPEs) and alternative plasticizers (APs). A case-control study was conducted to investigate whether exposures to OPEs, APs, and phthalates, were associated with uterine fibroids in women of reproductive age. For this purpose, the cases (n = 32) and the matching controls (n = 79) were chosen based on the results of gynecologic ultrasonography among premenopausal adult women in Korea and measured for metabolites of several OPEs, APs, and major phthalates. Logistic regression models were employed to assess the associations between chemical exposure and disease status. Factor analysis was conducted for multiple chemical exposure assessments as a secondary analysis. Among OPE metabolites, diphenyl phosphate (DPHP), 2-ethylhexyl phenyl phosphate (EHPHP), and 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP) were detected in >80% of the subjects. Among APs, metabolites of di-isononyl phthalate (DINP) and di(2-propylheptyl) phthalate (DPrHpP) were detected in >75% of the urine samples. The odds ratios (ORs) of uterine fibroids were significantly higher among the women with higher exposures to tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and tris(2-butoxyethyl) phosphate (TBOEP), di(2-ethylhexyl) terephthalate (DEHTP), DPrHpP, and di-(iso-nonyl)-cyclohexane-1,2-dicarboxylate (DINCH). In addition, urinary concentrations of mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), a sum of five di(2-ethylhexyl) phthalate metabolites (∑5DEHP), and mono(4-methyl-7-hydroxyoctyl) phthalate (OH-MINP) were significantly higher in the cases. In factor analysis, a factor heavily loaded with DPrHpP and DEHP was significantly associated with uterine fibroids, supporting the observation from the single chemical regression model. We found for the first time that several metabolites of OPEs and APs are associated with increased risks of uterine fibroids among pre-menopausal women. Further epidemiological and mechanistic studies are warranted to validate the associations observed in the present study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envres.2020.109874DOI Listing
October 2020

The migration of bisphenols from beverage cans and reusable sports bottles.

Food Chem 2020 Nov 18;331:127326. Epub 2020 Jun 18.

Jožef Stefan Institute, Jamova cesta 39, 1000 Ljubljana, Slovenia; International Postgraduate School Jožef Stefan, Jamova cesta 39, 1000 Ljubljana, Slovenia. Electronic address:

A precise and accurate GC-MS/MS method with ng L LLOQs, acceptable recovery (78-107%) and estimated uncertainty (U > 20%, except at LLOQ) was developed following the Eurachem guidelines. We established the migration and stability of twelve bisphenols in two food simulants (C: 20% ethanol, and B: 3% acetic acid) from beverage cans (n = 16) and reusable metal and plastic sports bottles (n = 51). Bisphenols were stable in dried (eight weeks, -20 °C) and derivatised extracts (seven days, 21 °C). Cans leached BPA (<5865 ng L), three BPF isomers (8.2-1286 ng L) and BPAP (1.6 ng L), while bottles leached BPA (<222 ng L) and BPF, BPE, BPB and BPZ (1.1-4.6 ng L). Simulant C was more aggressive than simulant B, and concentrations of bisphenols decreased with consecutive exposure to simulants. Levels of BPA migrating from cans did not exceed the specific migration limits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.foodchem.2020.127326DOI Listing
November 2020

Photochemical degradation of BPF, BPS and BPZ in aqueous solution: Identification of transformation products and degradation kinetics.

Sci Total Environ 2019 May 5;664:595-604. Epub 2019 Feb 5.

Jožef Stefan Institute, Jamova cesta 39, 1000 Ljubljana, Slovenia; International Postgraduate School Jožef Stefan, Jamova cesta 39, 1000 Ljubljana, Slovenia. Electronic address:

Bisphenols (BPs) are industrial chemicals that are used as monomers in the production of polycarbonate plastics and epoxy resins. These compounds can leach into the aqueous environment, where they can potentially have toxic effects. The aim of this study was to assess the photochemical degradation of three common bisphenols: BPF, BPS and BPZ in aqueous solution and determine their degradation kinetics and characterise their transformation products. Three independent experiments were performed based on: 1) direct photolysis using UV irradiation, 2) cyclodextrin-enhanced photolysis and 3) the photo-Fenton reaction. Analysis was performed using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography coupled to high-resolution quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS). This approach enabled for the first time a comparison between various conditions of photochemical degradation, revealing to be an effective way of removing (>90%) BPF, BPS and BPZ from aqueous samples. In all cases, degradation followed a pseudo-first order kinetic profile, while removal efficiency and formation of transformation products depended on the applied process. The photo-Fenton process resulted in the shortest half-lives (16.1 ̶ 21.7 min) and generated the highest number of transformation products. Overall, in this study we identified 11 novels and eight previously reported TPs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2019.02.064DOI Listing
May 2019

Current-use of developers in thermal paper from 14 countries using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

Toxicology 2019 03 8;416:54-61. Epub 2019 Feb 8.

Toxicological Centre, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium. Electronic address:

Thermal printing is a fast, widespread and inexpensive technology that uses a developer to produce a print on the paper, among many applications. A common developer is bisphenol A (BPA), used for this purpose in its free form. Consequently, the handling of thermal paper, as evaluated by the European Food Safety Authority, was reported to be the second largest source of external human exposure to this endocrine disrupting chemical. Recently, reports have been made on the substitution of BPA by alternative developers, which are yet less studied. In this study, 311 receipts and other thermal paper products were collected from 14 countries in Europe, Asia, North America and Oceania and analysed using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. BPA was the most frequently used main developer and was detected in 194 thermal paper samples, which represents a detection frequency of 63%. A statistically significant difference in the detection of BPA was shown between continents. BPA was followed by bisphenol S (BPS) which was detected in 64 samples as the main developer. Pergafast 201 was the third most abundant main developer and detected in 37 samples as the main developer. Less frequently used main developers included BPS-MAE, TGSA, d-8, and d-90, many of them being BPS derivatives. Two oligomers of d-90 (n = 1 and n = 2) were also identified. The sensitizer diphenyl sulphone (DPS) was identified using high-resolution mass spectrometry for the first time and detected in combination with other developers than BPS for the first time. Despite the lack of structural, nation-wide legislation prohibiting the use of BPA in thermal paper, it is clear that alternative developers are currently globally in use for the manufacturing of thermal paper.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tox.2019.02.003DOI Listing
March 2019

Suspect and non-target screening workflows to investigate the in vitro and in vivo metabolism of the synthetic cannabinoid 5Cl-THJ-018.

Drug Test Anal 2019 Mar 23;11(3):479-491. Epub 2018 Oct 23.

Toxicological Centre, University of Antwerp, Antwerp, Belgium.

The use of synthetic cannabinoids causes similar effects as Δ -tetrahydrocannabinol and long-term (ab)use can lead to health hazards and fatal intoxications. As most investigated synthetic cannabinoids undergo extensive biotransformation, almost no parent compound can be detected in urine, which hampers forensic investigations. Limited information about the biotransformation products of new synthetic cannabinoids makes the detection of these drugs in various biological matrices challenging. This study aimed to identify the main in vitro biotransformation pathways of 5Cl-THJ-018 and to compare these findings with an authentic urine sample of a 5Cl-THJ-018 user. The synthetic cannabinoid was incubated with pooled human liver microsomes and cytosol to simulate phase I and phase II biotransformations. Resulting extracts were analyzed with liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Three different data analysis workflows were applied to identify biotransformation products. A suspect screening workflow used an in-house database built from literature data and in silico biotransformation predictions. Two non-target screening workflows used a commercially available software and an open-source software for mass spectrometry data processing. A total of 23 in vitro biotransformation products were identified, with hydroxylation, oxidative dechlorination, and dihydrodiol formation pathways as the main phase I reactions. Additionally, five glucuronidated and three sulfated phase II conjugates were identified. The predominant in vivo pathway was through oxidative dechlorination and in total six metabolites of 5Cl-THJ-018 were identified. Biotransformation products both in vitro and in vivo were successfully identified using complementary suspect and non-target screening workflows.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/dta.2508DOI Listing
March 2019

Suspect and untargeted screening of bisphenol S metabolites produced by in vitro human liver metabolism.

Toxicol Lett 2018 Oct 18;295:115-123. Epub 2018 Jun 18.

Toxicological Centre, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium. Electronic address:

Bisphenol S (BPS) is increasingly used as substitute for bisphenol A, resulting in higher potential of human exposure to this compound. Yet, information on the human metabolism of BPS is limited. Hence, current biomonitoring studies rely only on the measurement of BPS itself, leading to a potential underestimation of assessing human exposure to this emerging contaminant. The aims of this study were to investigate the in vitro metabolic pathways of BPS using human liver microsomes and cytosol fractions and propose in vitro metabolites for evaluation in pharmacokinetics studies. Liquid chromatography coupled to quadrupole time-of-flight high-resolution mass spectrometry was used for the screening, identification, and structural elucidation of Phase I and II metabolites of BPS for the first time. Metabolite identification was performed using two complementary workflows: suspect and untargeted screening. Two Phase I metabolites were formed through hydroxylation of the phenolic rings. Four Phase II metabolites were formed through conjugation with glucuronic acid or sulfate. Three of these metabolites, namely dihydroxy-BPS, hydroxy-BPS-glucuronide and hydroxy-BPS-sulfate were identified and structurally elucidated for the first time. As such, we provide an expanded set of in vitro biotransformation products of BPS, which can potentially support a reliable assessment of BPS exposure in future biomonitoring studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.toxlet.2018.05.034DOI Listing
October 2018

In vitro Phase I and Phase II metabolism of the new designer benzodiazepine cloniprazepam using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

J Pharm Biomed Anal 2018 May 21;153:158-167. Epub 2018 Feb 21.

Toxicological Centre, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium.

Designer benzodiazepines have recently emerged as a class of new psychoactive substances. These substances are used in recreational settings and as alternatives to prescription benzodiazepines as self-medication for patients suffering from anxiety or other mental disorders. Due to the limited information available on the metabolic fate of these new substances, it is challenging to reliably detect their usage in bioanalytical (e.g. clinical and forensic) settings. The objective of this study was to investigate the in vitro Phase I and Phase II metabolism of the new designer benzodiazepine cloniprazepam and identify potential biomarkers for its detection in human biological fluids. Cloniprazepam was incubated with human liver microsomes and cytosolic fractions to generate both Phase I and II metabolites. The extracts were analysed using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Identification of the metabolites was performed using two complementary workflows, including a suspect screening based on in silico predictions and a non-targeted screening. A total of nine metabolites were identified, eight Phase I metabolites and one Phase II metabolite, of which five were specific for cloniprazepam. Clonazepam was the major metabolite of cloniprazepam. Hydroxy-cloniprazepam, dihydroxy-cloniprazepam, 3-keto-cloniprazepam, 7-amino-cloniprazepam, hydroxy-clonazepam, 7-amino-clonazepam and 3-hydroxy-7-amino-clonazepam were formed through oxidation, hydroxylation, and/or reduction of the nitro-group. Glucuronidated hydroxy-cloniprazepam was the only Phase II metabolite detected. Five metabolites were specific for cloniprazepam. This study provided a set of human in vitro biotransformation products which can assist specific detection of cloniprazepam consumption in future studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpba.2018.02.032DOI Listing
May 2018

A straightforward, validated liquid chromatography coupled to tandem mass spectrometry method for the simultaneous detection of nine drugs of abuse and their metabolites in hair and nails.

Anal Chim Acta 2017 Apr 25;960:101-109. Epub 2017 Jan 25.

Toxicological Centre, University of Antwerp, Universiteitsplein 1, B2610 Antwerp, Belgium; Toxicology and TDM Laboratory, ZNA Stuivenberg Hospital, Lange Beeldekenstraat 267, B2060 Antwerp, Belgium.

Hair and nails allow for a stable accumulation of compounds over time and retrospective investigation of past exposure and/or consumption. Owing to their long window of detection (weeks to months), analysis of these matrices can provide information complementary to blood and urine analysis or can be used in standalone when e.g. elimination from the body has already occurred. Drugs of abuse are often used together and, therefore, multi-analyte methods capable of detecting several substances and their metabolites in a single run are of importance. This paper presents the development and validation of a method based on liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) for the simultaneous detection of nine drugs of abuse and their metabolites in hair and nails. We focused on a simple and straightforward sample preparation to reduce costs, and allow application in routine laboratory practice. Chromatographic and mass spectrometric parameters, such as column type, mobile phase, and multiple reaction monitoring transitions were optimized. The method was validated according to the European Medicine Agency guidelines with an assessment of specificity, limit of quantification (LOQ), linearity, accuracy, precision, carry-over, matrix effects, recovery, and process efficiency. Linearity ranged from 25 to 20 000 pg mg hair and from 50 to 20 000 pg mg nails, and the lowest calibration point achieved the requirements for the LOQ (25 pg mg for hair and 50 pg mg for nails). Although it was not the main focus of the article, the reliability of the method was proven through successful participation in a proficiency test, and by investigation of authentic hair and nail samples from self-reported drug users. In the future, the method should allow comparison between the two matrices to acquire an in-depth knowledge of nail analysis and to define cutoff levels for nail analysis, as they exist for hair.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.aca.2017.01.022DOI Listing
April 2017