Innovative analytical methodologies for characterizing chemical exposure with a view to next-generation risk assessment.

The chemical burden on the environment and human population is increasing. Consequently, regulatory risk assessment must keep pace to manage, reduce, and prevent adverse impacts on human and environmental health associated with hazardous chemicals. Surveillance of chemicals of known, emerging, or potential future concern, entering the environment-food-human continuum is needed to document the reality of risks posed by chemicals on ecosystem and human health from a one health perspective, feed into early warning systems and support public policies for exposure mitigation provisions and safe and sustainable by design strategies. The use of less-conventional sampling strategies and integration of full-scan, high-resolution mass spectrometry and effect-directed analysis in environmental and human monitoring programmes have the potential to enhance the screening and identification of a wider range of chemicals of known, emerging or potential future concern. Here, we outline the key needs and recommendations identified within the European Partnership for Assessment of Risks from Chemicals (PARC) project for leveraging these innovative methodologies to support the development of next-generation chemical risk assessment.

HBM4EU E-waste study: Assessing persistent organic pollutants in blood, silicone wristbands, and settled dust among E-waste recycling workers in Europe.

E-waste recycling is an increasingly important activity that contributes to reducing the burden of end-of-life electronic and electrical apparatus and allows for the EU's transition to a circular economy. This study investigated the exposure levels of selected persistent organic pollutants (POPs) in workers from e-waste recycling facilities across Europe. The concentrations of seven polychlorinated biphenyls (PCBs) and eight polybrominated diphenyl ethers (PBDEs) congeners were measured by GC-MS. Workers were categorized into five groups based on the type of e-waste handled and two control groups. Generalized linear models were used to assess the determinants of exposure levels among workers. POPs levels were also assessed in dust and silicone wristbands (SWB) and compared with serum. Four PCB congeners (CB 118, 138, 153, and 180) were frequently detected in serum regardless of worker's category. With the exception of CB 118, all tested PCBs were significantly higher in workers compared to the control group. Controls working in the same company as occupationally exposed (Within control group), also displayed higher levels of serum CB 180 than non-industrial controls with no known exposures to these chemicals (Outwith controls) (p < 0.05). BDE 209 was the most prevalent POP in settled dust (16 µg/g) and SWB (220 ng/WB). Spearman correlation revealed moderate to strong positive correlations between SWB and dust. Increased age and the number of years smoked cigarettes were key determinants for workers exposure. Estimated daily intake through dust ingestion revealed that ΣPCB was higher for both the 50th (0.03 ng/kg bw/day) and 95th (0.09 ng/kg bw/day) percentile exposure scenarios compared to values reported for the general population. This study is one of the first to address the occupational exposure to PCBs and PBDEs in Europe among e-waste workers through biomonitoring combined with analysis of settled dust and SWB. Our findings suggest that e-waste workers may face elevated PCB exposure and that appropriate exposure assessments are needed to establish effective mitigation strategies.

Exposure of children to brominated flame retardants and heavy metals in Morocco: Urine and blood levels in association with global cytosine and adenine methylation.

Persistent pollutants, namely brominated flame retardants (BFRs) and heavy metals, are compounds that are added to a wide range of products and materials for preventing ignition, increasing the functionality of materials or improving their performance, e.g. electric conductivity. The exposure of children might consequently be inferred, through indoor dust and hand-to-mouth or toy-chewing behaviors. The current study is aimed at assessing the exposure of Moroccan children to BFRs and heavy metal elements, and evaluating their associations with global DNA methylation. First, parents responded to a questionnaire pertaining to children's lifestyle, then blood and urine samples were collected from (n = 93) children aged between 5 and 11 years for biomonitoring and DNA methylation analysis. BFRs were detected in 54.84% of samples with a median concentration of 0.01 nmol/mL (range: 0.004-0.051 nmol/mL) while metal elements were detected in more than 90% of samples. BFRs showed no variations with global DNA methylation, unlike metal elements, which revealed significant associations with global DNA methylation markers, namely 5-mC, 5-hmC and N6-mA levels. Moroccan children may be exposed to flame retardants and heavy metals through several routes. Further research is required to assess the exposure and the health impacts of environmental pollutants and ultimately protect the Moroccan population by the prevention of adverse health effects.

Degradation products of resin-based materials detected in saliva in vivo.

OBJECTIVES: Dental composites remain under scrutiny regarding their (long-term) safety. In spite of numerous studies on the release of monomers both in vitro and in vivo, only limited quantitative data exist on the in vivo leaching of degradation products from monomers and additives. The aim of this observational study was for the first time to quantitatively and qualitatively monitor the release of parent compounds and their degradation products in saliva from patients undergoing multiple restorations. MATERIALS AND METHODS: Five patients in need of multiple large composite restorations (minimally 5 up to 28 restorations) due to wear (attrition, abrasion, and erosion) were included in the study, and they received adhesive restorative treatment according to the standard procedures in the university clinic for Restorative Dentistry. Saliva was collected at different time points, starting before the restoration up until 24 h after the treatment with composite restorations. Saliva extracts were analyzed by liquid chromatography-mass spectrometry. RESULTS: Leaching of monomers and degradation products was highest within 30 min after the placement of the restorations. The highest median concentrations of monomers were recorded for UDMA, BisEMA-3, and TEGDMA; yet, besides BisEMA-3 and TEGDMA, no monomers could be detected after 24 h. Mono- and demethacrylated degradation products remained present up to 24 h and concentrations were generally higher than those of monomers. In patients with multiple restorations, degradation products were still present in the sample taken before the next operation, several weeks after the previous operation. CONCLUSIONS: Exposure to residual monomers and degradation products occurs in the first hours after restoration. Monomers are present in saliva shortly after restoration, but degradation products can be detected weeks after the restoration confirming a long-term release. CLINICAL SIGNIFICANCE: Future research should focus more on the release of degradation products from monomers and additives from resin-based materials given their prolonged presence in saliva after restoration.

Bombé, an undetermined substance that caused an outbreak of illicit drug use in Kinshasa, Democratic Republic of the Congo.

BACKGROUND: Illegal drugs are becoming a public health problem in African cities. In 2021, Bombé, a new drug of unknown composition, caused an outbreak of neuro-psychiatric symptoms in Kinshasa. Bombé was rumored to be based on ground catalytic exhausts stolen from cars. METHODS: The chemical composition of six samples of Bombé obtained from different neighborhoods in Kinshasa was determined by triple quad liquid chromatography-mass spectrometry/mass spectrometry with confirmation by quadrupole time-of-flight mass spectrometry. Metals were determined by inductively coupled plasma-mass spectrometry, and polycyclic aromatic hydrocarbons were measured by gas chromatography-mass spectrometry. RESULTS: Analysis of the Bombé samples revealed that it contained heroin (2-12% of the total area under the curve of the samples) and opioid derivatives, plus paracetamol (33-72%), caffeine (17-26%), and also benzodiazepines (5/6 samples) and cyproheptadine (2/6 samples). The concentrations of neurotoxic metals were unremarkable. The median (range) concentrations of manganese and lead were 9.4 µg/g (range 3-334 µg/g) and 0.36 µg/g (range 0.1-3.12 µg/g ), respectively. All polycyclic aromatic hydrocarbons were below the level of detection (<0.10 µg/g). CONCLUSION: Thanks to international collaboration, Bombé was documented to be a heroin-based drug and its alleged origin from catalytic exhausts was not substantiated. The local human expertise and technical capacity for undertaking toxicological analyses should be increased in Africa.

FAIR environmental and health registry (FAIREHR)- supporting the science to policy interface and life science research, development and innovation.

The environmental impact on health is an inevitable by-product of human activity. Environmental health sciences is a multidisciplinary field addressing complex issues on how people are exposed to hazardous chemicals that can potentially affect adversely the health of present and future generations. Exposure sciences and environmental epidemiology are becoming increasingly data-driven and their efficiency and effectiveness can significantly improve by implementing the FAIR (findable, accessible, interoperable, reusable) principles for scientific data management and stewardship. This will enable data integration, interoperability and (re)use while also facilitating the use of new and powerful analytical tools such as artificial intelligence and machine learning in the benefit of public health policy, and research, development and innovation (RDI). Early research planning is critical to ensuring data is FAIR at the outset. This entails a well-informed and planned strategy concerning the identification of appropriate data and metadata to be gathered, along with established procedures for their collection, documentation, and management. Furthermore, suitable approaches must be implemented to evaluate and ensure the quality of the data. Therefore, the 'Europe Regional Chapter of the International Society of Exposure Science' (ISES Europe) human biomonitoring working group (ISES Europe HBM WG) proposes the development of a FAIR Environment and health registry (FAIREHR) (hereafter FAIREHR). FAIR Environment and health registry offers preregistration of studies on exposure sciences and environmental epidemiology using HBM (as a starting point) across all areas of environmental and occupational health globally. The registry is proposed to receive a dedicated web-based interface, to be electronically searchable and to be available to all relevant data providers, users and stakeholders. Planned Human biomonitoring studies would ideally be registered before formal recruitment of study participants. The resulting FAIREHR would contain public records of metadata such as study design, data management, an audit trail of major changes to planned methods, details of when the study will be completed, and links to resulting publications and data repositories when provided by the authors. The FAIREHR would function as an integrated platform designed to cater to the needs of scientists, companies, publishers, and policymakers by providing user-friendly features. The implementation of FAIREHR is expected to yield significant benefits in terms of enabling more effective utilization of human biomonitoring (HBM) data.

Methods and Strategies for Biomonitoring in Occupational Exposure to Plant Protection Products Containing Glyphosate.

Glyphosate, and the ever growing reliance on its use in agriculture, has been a point of contention for many years. There have been debates regarding the risk and safety of using glyphosate-based herbicides as well as the effects of occupational, accidental, or systematic. Although there have been a number of studies conducted, the biomonitoring of glyphosate poses a series of challenges. Researchers attempting to determine the occupational exposure face questions regarding the most appropriate analytical techniques and sampling procedures. The present review aims to summarize and synthetize the analytical methodologies available and suitable for the purpose of glyphosate biomonitoring studies as well as discuss the advantages and disadvantages of each analytical technique, from the most modern to more well-established and older ones. The most relevant publications that have described analytical methods and published within the last 12 years were studied. Methods were compared, and the advantages and disadvantages of each methods were discussed. A total of 35 manuscripts describing analytical methods for glyphosate determination were summarized and discussed, with the most relevant one being compared. For methods that were not intended for biological samples, we discussed if they could be used for biomonitoring and approaches to adapt these methods for this purpose.

The HBM4EU chromates study - Outcomes and impacts on EU policies and occupational health practices.

Within the EU human biomonitoring initiative (HBM4EU), a targeted, multi-national study on occupational exposure to hexavalent chromium (Cr(VI)) was performed. Cr(VI) is currently regulated in EU under REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) and under occupational safety and health (OSH) legislation. It has recently been subject to regulatory actions to improve its risk management in European workplaces. Analysis of the data obtained within the HBM4EU chromates study provides support both for the implementation of these regulatory actions and for national enforcement programs and may also contribute to the updating of occupational limit values (OELs) and biological limit values for Cr(VI). It also provides useful insights on the contribution of different risk management measures (RMMs) to further reduce the exposure to Cr(VI) and may support the evaluation of applications for authorisation under REACH. Findings on chrome platers' additional per- and polyfluoroalkyl substances (PFAS) exposure highlight the need to also pay attention to this substance group in the metals sector. A survey performed to evaluate the policy relevance of the HBM4EU chromates study findings supports the usefulness of the study results. According to the responses received from the survey, the HBM4EU chromates study was able to demonstrate the added value of the human biomonitoring (HBM) approach in assessment and management of occupational exposure to Cr(VI). For future occupational studies, we emphasise the need for engagement of policy makers and regulators throughout the whole research process to ensure awareness, relevance and uptake of the results in future policies.

Exposure of children to glyphosate in Morocco: Urinary levels and predictors of exposure.

Glyphosate is one of the most frequently used organophosphorus plant protection products worldwide, and has recently been classified as probably carcinogenic to humans by the International Agency for Research and Cancer (IARC). We aimed to evaluate the urinary levels of glyphosate and its metabolite aminomethylphosphonic acid (AMPA) in Moroccan children, to identify the main predictors and to perform a risk assessment. Data was collected during a cross sectional study of 48 children from an intensive agricultural area. Measurements included a questionnaire on life-style, socio-demographic and herbicide exposures. Urinary glyphosate and AMPA were extracted using solid phase extraction (SPE) and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Overall, glyphosate and AMPA were detected in 73% and 75% of urine samples, respectively. The mean concentrations were 0.97 µg L-1 (2.06 µg/gcreatinine) for glyphosate and 0.79 µg L-1 (1.52 µg/gcreatinine) for AMPA. Children younger than 5 years had a higher AMPA and glyphosate urine concentration (mean = 2.24 µg L-1; estimation coefficient (EC) = 1.39; 95% CI: 0.54-2.24) (mean = 4.05 µg L-1; EC = 2.92; 95% CI: 1.68-4.15), respectively, than children aged 6-12. Children living near the pesticide spraying fields (<50 m) had 14.91 µg L-1 and 2.35 µg L-1 more glyphosate and AMPA, respectively, than children living in urban counties (95% CI: 8.14-20.91 for glyphosate and 95% CI: 0.55-4.14 for AMPA). AMPA concentration varied significantly with the source of drinking water, AMPA was higher among children that used water from open water sources (mean = 1.49 µg L-1; EC = 2.98; 95% CI/0.67-5.78) compared to those using water from closed water sources. There were also non-significant associations found, such as total household net income, current parental job description, and dietary intake. With the regard to the health risk assessment, estimated daily intake (EDIs), hazard quotient (HQs), and a hazard index (HI) were calculated. The GMs of EDI were 4.38 and 2.26 µg/kg of body weight BW/day for glyphosate and AMPA, respectively. The HQs were calculated considering 0.5 mg/kg BW/day as an acceptable daily intake (ADI), which EFSA has established as a health-based reference value for both analytes. The value obtained were lower than 1, and therefore, low health risk due to glyphosate and AMPA was expected for the target population under the study. This study provides further evidence on factors associated with glyphosate exposure, especially in developing countries.

Prenatal trimester-specific intake of micronutrients: global DNA methylation and hydroxymethylation at birth and persistence in childhood.

The prenatal environment may program health and disease susceptibility via epigenetic mechanisms. We evaluated associations of maternal trimester-specific intake of micronutrients with global DNA methylation (%5mC) and 5-hydroxymethylation (%5hmC) at birth in cord blood and tested for persistence into childhood. We quantified global %5mC and %5hmC in cord blood cells (n = 434) and in leukocytes collected in early (n = 108) and mid-childhood (n = 390) from children in Project Viva, a pre-birth cohort from Boston, MA. Validated food frequency questionnaires estimated maternal first- and second-trimester intakes of vitamin B2, vitamin B6, vitamin B12, folate, betaine, choline, methionine, iron, and zinc. Mean (SD) cord blood %5mC and %5hmC was 5.62% (2.04) and 0.25% (0.15), respectively. Each µg increase in first-trimester B12 intake was associated with 0.002 lower %5hmC in cord blood (95% CI: -0.005, -0.0003), and this association persisted in early childhood (ß = -0.007; 95% CI: -0.01, -0.001) but not mid-childhood. Second-trimester iron (mg) was associated with 0.01 lower %5mC (95% CI: -0.02, -0.002) and 0.001 lower %5hmC (95% CI: -0.01, -0.00001) in cord blood only. Increased second-trimester zinc (mg) intake was associated with 0.003 greater %5hmC in early childhood (ß = 0.003; 95% CI: 0.0004, 0.006). Second-trimester folate was positively associated with %5hmC in early childhood only (ß = 0.08, 95% CI: 0.003, 0.16). Associations did not survive multiple testing adjustment; future replication is needed. Trimester-specific nutrients may impact various sensitive windows of epigenetic programming some with lasting effects in childhood. Further research is needed to understand the role of gene-specific epigenetic changes and how global DNA methylation measures relate to child health.

Interpreting biomonitoring data: Introducing the international human biomonitoring (i-HBM) working group's health-based guidance value (HB2GV) dashboard.

Human biomonitoring (HBM) data measured in specific contexts or populations provide information for comparing population exposures. There are numerous health-based biomonitoring guidance values, but to locate these values, interested parties need to seek them out individually from publications, governmental reports, websites and other sources. Until now, there has been no central, international repository for this information. Thus, a tool is needed to help researchers, public health professionals, risk assessors, and regulatory decision makers to quickly locate relevant values on numerous environmental chemicals. A free, on-line repository for international health-based guidance values to facilitate the interpretation of HBM data is now available. The repository is referred to as the "Human Biomonitoring Health-Based Guidance Value (HB2GV) Dashboard". The Dashboard represents the efforts of the International Human Biomonitoring Working Group (i-HBM), affiliated with the International Society of Exposure Science. The i-HBM's mission is to promote the use of population-level HBM data to inform public health decision-making by developing harmonized resources to facilitate the interpretation of HBM data in a health-based context. This paper describes the methods used to compile the human biomonitoring health-based guidance values, how the values can be accessed and used, and caveats with using the Dashboard for interpreting HBM data. To our knowledge, the HB2GV Dashboard is the first open-access, curated database of HBM guidance values developed for use in interpreting HBM data. This new resource can assist global HBM data users such as risk assessors, risk managers and biomonitoring programs with a readily available compilation of guidance values.

Developing human biomonitoring as a 21st century toolbox within the European exposure science strategy 2020-2030.

Human biomonitoring (HBM) is a crucial approach for exposure assessment, as emphasised in the European Commission's Chemicals Strategy for Sustainability (CSS). HBM can help to improve chemical policies in five major key areas: (1) assessing internal and aggregate exposure in different target populations; 2) assessing exposure to chemicals across life stages; (3) assessing combined exposure to multiple chemicals (mixtures); (4) bridging regulatory silos on aggregate exposure; and (5) enhancing the effectiveness of risk management measures. In this strategy paper we propose a vision and a strategy for the use of HBM in chemical regulations and public health policy in Europe and beyond. We outline six strategic objectives and a roadmap to further strengthen HBM approaches and increase their implementation in the regulatory risk assessment of chemicals to enhance our understanding of exposure and health impacts, enabling timely and targeted policy interventions and risk management. These strategic objectives are: 1) further development of sampling strategies and sample preparation; 2) further development of chemical-analytical HBM methods; 3) improving harmonisation throughout the HBM research life cycle; 4) further development of quality control / quality assurance throughout the HBM research life cycle; 5) obtain sustained funding and reinforcement by legislation; and 6) extend target-specific communication with scientists, policymakers, citizens and other stakeholders. HBM approaches are essential in risk assessment to address scientific, regulatory and societal challenges. HBM requires full and strong support from the scientific and regulatory domain to reach its full potential in public and occupational health assessment and in regulatory decision-making.

The Use of Human Biomonitoring to Assess Occupational Exposure to PAHs in Europe: A Comprehensive Review.

Polycyclic aromatic hydrocarbons (PAHs) are among the chemicals with proven impact on workers' health. The use of human biomonitoring (HBM) to assess occupational exposure to PAHs has become more common in recent years, but the data generated need an overall view to make them more usable by regulators and policymakers. This comprehensive review, developed under the Human Biomonitoring for Europe (HBM4EU) Initiative, was based on the literature available from 2008-2022, aiming to present and discuss the information on occupational exposure to PAHs, in order to identify the strengths and limitations of exposure and effect biomarkers and the knowledge needs for regulation in the workplace. The most frequently used exposure biomarker is urinary 1-hydroxypyrene (1-OH-PYR), a metabolite of pyrene. As effect biomarkers, those based on the measurement of oxidative stress (urinary 8-oxo-dG adducts) and genotoxicity (blood DNA strand-breaks) are the most common. Overall, a need to advance new harmonized approaches both in data and sample collection and in the use of appropriate biomarkers in occupational studies to obtain reliable and comparable data on PAH exposure in different industrial sectors, was noted. Moreover, the use of effect biomarkers can assist to identify work environments or activities of high risk, thus enabling preventive risk mitigation and management measures.

HBM4EU Chromates Study-Genotoxicity and Oxidative Stress Biomarkers in Workers Exposed to Hexavalent Chromium.

A study was conducted within the European Human Biomonitoring Initiative (HBM4EU) to characterize occupational exposure to Cr(VI). Herein we present the results of biomarkers of genotoxicity and oxidative stress, including micronucleus analysis in lymphocytes and reticulocytes, the comet assay in whole blood, and malondialdehyde and 8-oxo-2'-deoxyguanosine in urine. Workers from several Cr(VI)-related industrial activities and controls from industrial (within company) and non-industrial (outwith company) environments were included. The significantly increased genotoxicity (p = 0.03 for MN in lymphocytes and reticulocytes; p < 0.001 for comet assay data) and oxidative stress levels (p = 0.007 and p < 0.001 for MDA and 8-OHdG levels in pre-shift urine samples, respectively) that were detected in the exposed workers over the outwith company controls suggest that Cr(VI) exposure might still represent a health risk, particularly, for chrome painters and electrolytic bath platers, despite the low Cr exposure. The within-company controls displayed DNA and chromosomal damage levels that were comparable to those of the exposed group, highlighting the relevance of considering all industry workers as potentially exposed. The use of effect biomarkers proved their capacity to detect the early biological effects from low Cr(VI) exposure, and to contribute to identifying subgroups that are at higher risk. Overall, this study reinforces the need for further re-evaluation of the occupational exposure limit and better application of protection measures. However, it also raised some additional questions and unexplained inconsistencies that need follow-up studies to be clarified.

HBM4EU Diisocyanates Study-Research Protocol for a Collaborative European Human Biological Monitoring Study on Occupational Exposure.

Diisocyanates have long been a leading cause of occupational asthma in Europe, and recently, they have been subjected to a restriction under the REACH regulations. As part of the European Human Biomonitoring project (HBM4EU), we present a study protocol designed to assess occupational exposure to diisocyanates in five European countries. The objectives of the study are to assess exposure in a number of sectors that have not been widely reported on in the past (for example, the manufacturing of large vehicles, such as in aerospace; the construction sector, where there are potentially several sources of exposure (e.g., sprayed insulation, floor screeds); the use of MDI-based glues, and the manufacture of spray adhesives or coatings) to test the usability of different biomarkers in the assessment of exposure to diisocyanates and to provide background data for regulatory purposes. The study will collect urine samples (analysed for diisocyanate-derived diamines and acetyl-MDI-lysine), blood samples (analysed for diisocyanate-specific IgE and IgG antibodies, inflammatory markers, and diisocyanate-specific Hb adducts for MDI), and buccal cells (micronucleus analysis) and measure fractional exhaled nitric oxide. In addition, occupational hygiene measurements (air monitoring and skin wipe samples) and questionnaire data will be collected. The protocol is harmonised across the participating countries to enable pooling of data, leading to better and more robust insights and recommendations.

HBM4EU chromates study - Usefulness of measurement of blood chromium levels in the assessment of occupational Cr(VI) exposure.

Occupational exposures to hexavalent Chromium (Cr(VI)) can occur in welding, hot working stainless steel processing, chrome plating, spray painting and coating activities. Recently, within the human biomonitoring for Europe initiative (HBM4EU), a study was performed to assess the suitability of different biomarkers to assess the exposure to Cr(VI) in various job tasks. Blood-based biomarkers may prove useful when more specific information on systemic and intracellular bioavailability is necessary. To this aim, concentrations of Cr in red blood cells (RBC-Cr) and in plasma (P-Cr) were analyzed in 345 Cr(VI) exposed workers and 175 controls to understand how these biomarkers may be affected by variable levels of exposure and job procedures. Compared to controls, significantly higher RBC-Cr levels were observed in bath plating and paint application workers, but not in welders, while all the 3 groups had significantly greater P-Cr concentrations. RBC-Cr and P-Cr in chrome platers showed a high correlation with Cr(VI) in inhalable dust, outside respiratory protective equipment (RPE), while such correlation could not be determined in welders. In platers, the use of RPE had a significant impact on the relationship between blood biomarkers and Cr(VI) in inhalable and respirable dust. Low correlations between P-Cr and RBC-Cr may reflect a difference in kinetics. This study showed that Cr-blood-based biomarkers can provide information on how workplace exposure translates into systemic availability of Cr(III) (extracellular, P-Cr) and Cr(VI) (intracellular, RBC-Cr). Further studies are needed to fully appreciate their use in an occupational health and safety context.

Quantification of three antineoplastic agents in urine using the UniSpray ionisation source.

BACKGROUND: Many guidelines and safety measures led to a decrease in exposure to antineoplastic agents. Since healthcare workers are often exposed to lower concentrations than patients, a sensitive method is needed to quantify occupational exposure. OBJECTIVE: The aim of this study was to develop and validate a sensitive method for simultaneous detection and quantification of cyclophosphamide, ifosfamide and paclitaxel in urine by use of UPLC-MS/MS with a UniSpray ionisation source. METHODS: Compounds were extracted from urine using Novum simplified liquid extraction cartridges, separated on a C18 column, ionised by a UniSpray ionisation source and detected with MS/MS. In the second part of the study, a field study was performed to assess occupational exposure to antineoplastic agents. RESULTS: Eighty-three samples from healthcare workers were analysed and resulted in seventeen samples containing quantifiable concentrations of at least one compound. In conclusion, a sensitive method for simultaneous detection and quantification of cyclophosphamide (LLOQ 0.05 ng/mL), ifosfamide (LLOQ 0.3 ng/mL) and paclitaxel (LLOQ 0.7 ng/mL) was developed and validated.

Surveillance of Indoor Air Concentration of Volatile Organic Compounds in Luxembourgish Households.

Exposure to air pollution is a well-known health risk. For instance, volatile and very volatile organic compounds (VOCs and VVOCs) are known to cause respiratory, haematologic or immune diseases, and even cancer. Based on the Luxembourgish indoor pollution surveillance program, we performed an exploratory analysis for the period 2014-2019, in order (1) to evaluate the prevalence of VOCs and VVOCs in households, and (2) to estimate the risks of lifelong exposure to selected VOCs on the health of the adult population. The database included 715 indoor air samples from 159 different households. Observed VOC and VVOC levels were similar to those in neighbouring countries. Our health impact assessment identified some health risks associated with the observed concentrations in Luxembourg. Furthermore, this study shows the major public health importance of having a national indoor pollution surveillance system in place. Highlights: (1) This study provides an overview of the domestic indoor pollution in Luxembourg. (2) (V)VOCs levels in Luxembourg were similar to those in neighbouring countries. (3) The results clearly show the importance of having a surveillance system in place.

HBM4EU Chromates Study: Urinary Metabolomics Study of Workers Exposed to Hexavalent Chromium.

Exposure to hexavalent chromium Cr(VI) may occur in several occupational activities, placing workers in many industries at risk for potential related health outcomes. Untargeted metabolomics was applied to investigate changes in metabolic pathways in response to Cr(VI) exposure. We obtained our data from a study population of 220 male workers with exposure to Cr(VI) and 102 male controls from Belgium, Finland, Poland, Portugal and the Netherlands within the HBM4EU Chromates Study. Urinary metabolite profiles were determined using liquid chromatography mass spectrometry, and differences between post-shift exposed workers and controls were analyzed using principal component analysis. Based on the first two principal components, we observed clustering by industrial chromate application, such as welding, chrome plating, and surface treatment, distinct from controls and not explained by smoking status or alcohol use. The changes in the abundancy of excreted metabolites observed in workers reflect fatty acid and monoamine neurotransmitter metabolism, oxidative modifications of amino acid residues, the excessive formation of abnormal amino acid metabolites and changes in steroid and thyrotropin-releasing hormones. The observed responses could also have resulted from work-related factors other than Cr(VI). Further targeted metabolomics studies are needed to better understand the observed modifications and further explore the suitability of urinary metabolites as early indicators of adverse effects associated with exposure to Cr(VI).

HBM4EU Chromates Study: Determinants of Exposure to Hexavalent Chromium in Plating, Welding and Other Occupational Settings.

Work-related exposures in industrial processing of chromate (chrome plating, surface treatment and welding) raise concern regarding the health risk of hexavalent chromium (Cr(VI)). In this study, performed under the HBM4EU project, we focused on better understanding the determinants of exposure and recognising how risk management measures (RMMs) contribute to a reduction in exposure. HBM and occupational hygiene data were collected from 399 workers and 203 controls recruited in nine European countries. Urinary total chromium (U-Cr), personal inhalable and respirable dust of Cr and Cr(VI) and Cr from hand wipes were collected. Data on the RMMs were collected by questionnaires. We studied the association between different exposure parameters and the use of RMMs. The relationship between exposure by inhalation and U-Cr in different worker groups was analysed using regression analysis and found a strong association. Automatisation of Cr electroplating dipping explained lower exposure levels in platers. The use of personal protective equipment resulted in lower U-Cr levels in welding, bath plating and painting. An effect of wearing gloves was observed in machining. An effect of local exhaust ventilation and training was observed in welding. Regression analyses showed that in platers, exposure to air level of 5 µg/m3 corresponds to U-Cr level of 7 µg/g creatinine. In welders, the same inhalation exposure resulted in lower U-Cr levels reflecting toxicokinetic differences of different chromium species.