HBM4EU chromates study - PFAS exposure in electroplaters and bystanders.

The study aims to reveal the exposure to perfluoroalkyl substances (PFAS) in workers in different industry sectors with exposures to hexavalent chromium (Cr(VI)). The PFAS exposure of in total 172 individuals from 4 countries was assessed by the determination of 8 perfluoroalkyl carboxylic acids and 4 perfluoroalkyl sulfonic acids in plasma samples. The participants were 52 chrome plating workers, 43 welders, 3 surface treating workers and 74 workers without any occupational Cr exposure as controls. Significant differences between workers with Cr exposure and controls were found for the perfluoroalkyl sulfonic acids, particularly for perfluorooctane sulfonic acid (PFOS). The median and maximum levels were, respectively, 4.83 and 789 µg/l for chrome plating workers, 4.97 and 1513 µg/l for welders, and 3.65 and 13.9 µg/l for controls. The considerably high PFOS exposure in Cr platers and welders can be explained by the former application of PFOS as mist suppressants in electroplating baths, which resulted in an exposure of the directly involved operators, but also of welders performing maintenance and repair service at these workplaces.

Occupational Exposure to Antineoplastic Drugs in Twelve French Health Care Setting: Biological Monitoring and Surface Contamination.

Antineoplastic drugs used in the treatment of cancers have an intrinsic toxicity, because of their genotoxic, teratogenic, and carcinogenic properties. Their use is recognized as an occupational hazard for healthcare workers (HCWs) who may be exposed. The purpose of this article is to present biological- and environmental-monitoring data collected in twelve French hospitals over eight years. Urine samples were collected from a wide range of HCWs (250 participants) from pharmacy and oncology units, including physicians, pharmacists, pharmacy technicians, nurses, auxiliary nurses, and cleaners. The investigated drugs were cyclophosphamide, ifosfamide, methotrexate, and α-fluoro-ß-alanine, the main urinary metabolite of 5-fluorouracil. Wipe samples were collected from various locations in pharmacy and oncology units. More than 50% of participants, from all exposure groups, were contaminated with either drug, depending on the unit, the day, or the task performed. However, workers from oncology units were more frequently exposed than workers from pharmacy units. Significant contamination was detected on various surfaces in pharmacy and oncology units, highlighting potential sources of exposure. Risk-management measures should be implemented to reduce and maintain exposures at lowest-possible levels. In addition, regular exposure assessment, including biological and environmental monitoring, is recommended to ensure the long-term efficiency of the prevention measures.

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.

HBM4EU chromates study - the measurement of hexavalent and trivalent chromium in exhaled breath condensate samples from occupationally exposed workers across Europe.

The aim of this study was to investigate the practicability of exhaled breath condensate (EBC) as a biological matrix to detect and measure hexavalent chromium (Cr(VI)) and trivalent chromium (Cr(III)) in workers occupationally exposed to Cr(VI). EBC samples were collected from workers in France, Finland, Italy, The Netherlands and the United Kingdom from three different target activities: chrome platers, stainless steel welders and surface treatment workers. Pre and post working week EBC samples were collected from 177 exposed workers and 98 unexposed workers (control group). Hyphenated chromatography systems with inductively coupled plasma - mass spectrometry (ICP-MS) were for the analysis. The results showed that the occupationally exposed workers had significantly higher levels of Cr(VI) and Cr(III) than the control group. Chrome platers exhibited the highest Cr(VI) levels in their EBC samples, with a significant increase from their pre to post samples for both Cr(VI) and Cr(III). A significant difference was also found between pre and post EBC samples for Cr(III) in welders. This study has shown that EBC has the potential to be a valid, non-invasive biological matrix to assess occupational exposure to Cr(VI) and Cr(III) for biological monitoring assessment, with the ability to detect low level inhalation exposures.

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.

Occupational exposure to metals among battery recyclers in France: Biomonitoring and external dose measurements.

In battery-recycling facilities, exposure to trace elements may occur through inhalation of contaminated dust or vapor emanating from the treatment processes. Exposure of battery-recycling workers to lead has been quite well covered in the literature. In contrast, we lack data on exposure to other elements contained in batteries. The aim of this study was to characterize the exposure of French battery recyclers to multiple elements using biomonitoring and airborne measurements. Eighty-six workers participated in the study. Inhalable metal concentrations were determined for personal airborne samples, and total exposure was determined from pre-shift and post-shift urine samples collected during the working week. In both types of sample, a total of 33 trace elements were measured using inductively coupled plasma mass spectrometry. Results showed battery recyclers to be mostly exposed to Cd, Co, Cr, Li, Mn, Ni, and Pb. Administrative and sorting workers were exposed at lower levels than maintenance, treatment, and dismantling workers. Cd, Co, Li, Mn, and Ni were detected at high levels in air samples, especially near the treatment facilities, with airborne cadmium levels of up to 79.4 µg/m3. Urinary sample analysis indicated exposure to Cd and Co, with levels measured at up to 27.6 and 3.34 µg/g of creatinine, respectively. Concentrations were compared to data reported for e-waste recycling companies. The data presented provide valuable information on exposure to trace elements for workers involved in battery-recycling. They also highlight the need to improve both collective and individual protective measures, which were not sufficient in the participating companies.

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.

Providing Biological Plausibility for Exposure-Health Relationships for the Mycotoxins Deoxynivalenol (DON) and Fumonisin B1 (FB1) in Humans Using the AOP Framework.

Humans are chronically exposed to the mycotoxins deoxynivalenol (DON) and fumonisin B1 (FB1), as indicated by their widespread presence in foods and occasional exposure in the workplace. This exposure is confirmed by human biomonitoring (HBM) studies on (metabolites of) these mycotoxins in human matrices. We evaluated the exposure-health relationship of the mycotoxins in humans by reviewing the available literature. Since human studies did not allow the identification of unequivocal chronic health effects upon exposure to DON and FB1, the adverse outcome pathway (AOP) framework was used to structure additional mechanistic evidence from in vitro and animal studies on the identified adverse effects. In addition to a preliminary AOP for DON resulting in the adverse outcome (AO) 'reduced body weight gain', we developed a more elaborated AOP for FB1, from the molecular initiating event (MIE) 'inhibition of ceramide synthases' leading to the AO 'neural tube defects'. The mechanistic evidence from AOPs can be used to support the limited evidence from human studies, to focus FB1- and DON-related research in humans to identify related early biomarkers of effect. In order to establish additional human exposure-health relationships in the future, recommendations are given to maximize the information that can be obtained from HBM.

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.

HBM4EU chromates study - Overall results and recommendations for the biomonitoring of occupational exposure to hexavalent chromium.

Exposure to hexavalent chromium [Cr(VI)] may occur in several occupational activities, e.g., welding, Cr(VI) electroplating and other surface treatment processes. The aim of this study was to provide EU relevant data on occupational Cr(VI) exposure to support the regulatory risk assessment and decision-making. In addition, the capability and validity of different biomarkers for the assessment of Cr(VI) exposure were evaluated. The study involved nine European countries and involved 399 workers in different industry sectors with exposures to Cr(VI) such as welding, bath plating, applying or removing paint and other tasks. We also studied 203 controls to establish a background in workers with no direct exposure to Cr(VI). We applied a cross-sectional study design and used chromium in urine as the primary biomonitoring method for Cr(VI) exposure. Additionally, we studied the use of red blood cells (RBC) and exhaled breath condensate (EBC) for biomonitoring of exposure to Cr(VI). Personal measurements were used to study exposure to inhalable and respirable Cr(VI) by personal air sampling. Dermal exposure was studied by taking hand wipe samples. The highest internal exposures were observed in the use of Cr(VI) in electrolytic bath plating. In stainless steel welding the internal Cr exposure was clearly lower when compared to plating activities. We observed a high correlation between chromium urinary levels and air Cr(VI) or dermal total Cr exposure. Urinary chromium showed its value as a first approach for the assessment of total, internal exposure. Correlations between urinary chromium and Cr(VI) in EBC and Cr in RBC were low, probably due to differences in kinetics and indicating that these biomonitoring approaches may not be interchangeable but rather complementary. This study showed that occupational biomonitoring studies can be conducted successfully by multi-national collaboration and provide relevant information to support policy actions aiming to reduce occupational exposure to chemicals.

HBM4EU Occupational Biomonitoring Study on e-Waste-Study Protocol.

Workers involved in the processing of electronic waste (e-waste) are potentially exposed to toxic chemicals. If exposure occurs, this may result in uptake and potential adverse health effects. Thus, exposure surveillance is an important requirement for health risk management and prevention of occupational disease. Human biomonitoring by measurement of specific biomarkers in body fluids is considered as an effective method of exposure surveillance. The aim of this study is to investigate the internal exposure of workers processing e-waste using a human biomonitoring approach, which will stimulate improved work practices and contribute to raising awareness of potential hazards. This exploratory study in occupational exposures in e-waste processing is part of the European Human Biomonitoring Initiative (HBM4EU). Here we present a study protocol using a cross sectional survey design to study worker's exposures and compare these to the exposure of subjects preferably employed in the same company but with no known exposure to industrial recycling of e-waste. The present study protocol will be applied in six to eight European countries to ensure standardised data collection. The target population size is 300 exposed and 150 controls. Biomarkers of exposure for the following chemicals will be used: chromium, cadmium and lead in blood and urine; brominated flame retardants and polychlorobiphenyls in blood; mercury, organophosphate flame retardants and phthalates in urine, and chromium, cadmium, lead and mercury in hair. In addition, the following effect biomarkers will be studied: micronuclei, epigenetic, oxidative stress, inflammatory markers and telomere length in blood and metabolomics in urine. Occupational hygiene sampling methods (airborne and settled dust, silicon wristbands and handwipes) and contextual information will be collected to facilitate the interpretation of the biomarker results and discuss exposure mitigating interventions to further reduce exposures if needed. This study protocol can be adapted to future European-wide occupational studies.

Mycotoxins Exposure of French Grain Elevator Workers: Biomonitoring and Airborne Measurements.

It is now recognized that additional exposure to mycotoxins may occur through inhalation of contaminated dust at a workplace. The aim of this study was to characterize the multi-mycotoxin exposure of French grain elevator workers using biomonitoring and airborne measurements. Eighteen workers participated in the study. Personal airborne dust samples were analyzed for their mycotoxin concentrations. Workers provided multiple urine samples including pre-shift, post-shift and first morning urine samples or 24 h urine samples. Mycotoxin urinary biomarkers (aflatoxin B1, aflatoxin M1, ochratoxin A, ochratoxin α, deoxynivalenol, zearalenone, α-zearalenol, ß-zearalenol, fumonisin B1, HT-2 toxin and T-2 toxin) were measured using a liquid chromatography-high-resolution mass spectrometry method. Grain elevator workers were highly exposed to organic airborne dust (median 4.92 mg.m-3). DON, ZEN and FB1 were frequent contaminants in 54, 76 and 72% of air samples, respectively. The mycotoxin biomarkers quantified were DON (98%), ZEN (99%), α-ZEL (52%), ß-ZEL (33%), OTA (76%), T-2 (4%) and HT-2 (4%). DON elimination profiles showed highest concentrations in samples collected after the end of the work shift and the urinary DON concentrations were significantly higher in post-shift than in pre-shift-samples (9.9 and 22.1 µg/L, respectively). ZEN and its metabolites concentrations did not vary according to the sampling time. However, the levels of α-/ß-ZEL were consistent with an additional occupational exposure. These data provide valuable information on grain worker exposure to mycotoxins. They also highlight the usefulness of multi-mycotoxin methods in assessing external and internal exposures, which shed light on the extent and pathways of exposure occurring in occupational settings.

Is the blood of a surgeon performing HIPEC contaminated by irinotecan, its major metabolites and platinum compounds?

OBJECTIVES: Hyperthermic intraperitoneal chemotherapy (HIPEC) is a beneficial surgical technique for patients, but the surgeons are being exposed to cytotoxic drugs. Few biomonitoring studies were led on blood samples in the context of HIPEC. This study aimed to evaluate the surgeon's plasmatic and red blood cell (RBC) contamination by irinotecan, two of its major metabolites and platinum compounds. METHODS: HIPEC procedures performed using the coliseum techniques were observed between September 2015 and April 2018 in a French comprehensive cancer center. Irinotecan and its metabolites SN-38 and APC were dosed by UHPLC with a limit of quantification determined at 50 pg/mL. Platinum compounds were dosed by inductively coupled plasma mass spectrometry with a limit of quantification determined at 16 pg/mL. RESULTS: Despite collective and personal protective equipment, 80% of plasma samples were contaminated by irinotecan and 33% by platinum compounds out of 21. The results showed that the surgeon was contaminated after HIPEC and even after a period of HIPEC inactivity. Nineteen percent of plasmatic samples and 45% of RBC samples were contaminated by SN-38, the active metabolite of irinotecan. APC was only found in some RBC samples (33%). CONCLUSIONS: Even if this study shows blood contamination by irinotecan, two of its major metabolites (including active SN-38) and platinum compounds both in the plasma and RBC of a surgeon performing the HIPEC procedures, further studies should be performed to confirm these results. Additional studies should be carried out to further investigate the contamination in the context of HIPEC and more broadly in the hospital.

Biomonitoring of occupational exposure to bisphenol A, bisphenol S and bisphenol F: A systematic review.

Bisphenol A (BPA) and its substitutes bisphenol S (BPS) and bisphenol F (BPF) are endocrine disrupting chemicals widely used in the production of polycarbonate plastics, epoxy resins and thermal papers. The aim of the review was to identify occupational studies using human biomonitoring (HBM) as a tool for bisphenol exposure assessment and to characterize research gaps on the topic as part of the HBM4EU project. Hence, a systematic literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was conducted for articles published between 2000 and 27th March 2020 across three databases (PubMed, Scopus and Web of Science). Thirty studies on the occupational HBM of BPA met the inclusion criteria. Regarding BPS and BPF, only 4 and 2 publications were retrieved, respectively. Fifty-seven percent (57%) of the studies selected for BPA were conducted in Asia whereas half of BPS and BPF studies were undertaken in Europe. Studies on BPA in plastic and epoxy resin sectors were infrequent in Europe while Asian data showed higher exposure when the substance is employed as raw material. The main data on BPS were among cashiers while BPF data were available from incinerator workers. Several research gaps have been identified: (i) shortage of HBM studies on occupational exposure, especially to BPS and BPF; (ii) different methodological designs making suitable comparisons between studies difficult; and (iii) only few studies conducted on the industrial applications of bisphenols outside Asia. This review highlights the lack of recent occupational HBM studies on bisphenols and the need for a harmonized approach to acquire reliable data. Considering the increasing replacement of BPA by BPS and BPF, it is of relevance to evaluate the exposure to these substances and the impact of the available risk management measures on workers exposure and possible health risk.

Biomarkers of effect as determined in human biomonitoring studies on hexavalent chromium and cadmium in the period 2008-2020.

A number of human biomonitoring (HBM) studies have presented data on exposure to hexavalent chromium [Cr(VI)] and cadmium (Cd), but comparatively few include results on effect biomarkers. The latter are needed to identify associations between exposure and adverse outcomes (AOs) in order to assess public health implications. To support improved derivation of EU regulation and policy making, it is of great importance to identify the most reliable effect biomarkers for these heavy metals that can be used in HBM studies. In the framework of the Human Biomonitoring for Europe (HBM4EU) initiative, our study aim was to identify effect biomarkers linking Cr(VI) and Cd exposure to selected AOs including cancer, immunotoxicity, oxidative stress, and omics/epigenetics. A comprehensive PubMed search identified recent HBM studies, in which effect biomarkers were examined. Validity and applicability of the markers in HBM studies are discussed. The most frequently analysed effect biomarkers regarding Cr(VI) exposure and its association with cancer were those indicating oxidative stress (e.g., 8-hydroxy-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA), glutathione (GSH)) and DNA or chromosomal damage (comet and micronucleus assays). With respect to Cd and to some extent Cr, ß-2-microglobulin (B2-MG) and N-acetyl-ß-D-glucosaminidase (NAG) are well-established, sensitive, and the most common effect biomarkers to relate Cd or Cr exposure to renal tubular dysfunction. Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule (KIM)-1 could serve as sensitive biomarkers of acute kidney injury in response to both metals, but need further investigation in HBM studies. Omics-based biomarkers, i.e., changes in the (epi-)genome, transcriptome, proteome, and metabolome associated with Cr and/or Cd exposure, are promising effect biomarkers, but more HBM data are needed to confirm their significance. The combination of established effect markers and omics biomarkers may represent the strongest approach, especially if based on knowledge of mechanistic principles. To this aim, also mechanistic data were collected to provide guidance on the use of more sensitive and specific effect biomarkers. This also led to the identification of knowledge gaps relevant to the direction of future research.

HBM4EU chromates study - Reflection and lessons learnt from designing and undertaking a collaborative European biomonitoring study on occupational exposure to hexavalent chromium.

The EU human biomonitoring initiative, HBM4EU, aims to co-ordinate and advance human biomonitoring (HBM) across Europe. As part of HBM4EU, we presented a protocol for a multicentre study to characterize occupational exposure to hexavalent chromium (Cr(VI)) in nine European countries (HBM4EU chromates study). This study intended to collect data on current occupational exposure and to test new indicators for chromium (Cr) biomonitoring (Cr(VI) in exhaled breath condensate and Cr in red blood cells), in addition to traditional urinary total Cr analyses. Also, data from occupational hygiene samples and biomarkers of early biological effects, including genetic and epigenetic effects, was obtained, complementing the biomonitoring information. Data collection and analysis was completed, with the project findings being made separately available. As HBM4EU prepares to embark on further European wide biomonitoring studies, we considered it important to reflect on the experiences gained through our harmonised approach. Several practical aspects are highlighted for improvement in future studies, e.g., more thorough/earlier training on the implementation of standard operating procedures for field researchers, training on the use of the data entry template, as well as improved company communications. The HBM4EU chromates study team considered that the study had successfully demonstrated the feasibility of conducting a harmonised multicentre investigation able to achieve the research aims and objectives. This was largely attributable to the engaged multidisciplinary network, committed to deliver clearly understood goals. Such networks take time and investment to develop, but are priceless in terms of their ability to deliver and facilitate knowledge sharing and collaboration.

Investigating Multi-Mycotoxin Exposure in Occupational Settings: A Biomonitoring and Airborne Measurement Approach.

Investigating workplace exposure to mycotoxins is of the utmost importance in supporting the implementation of preventive measures for workers. The aim of this study was to provide tools for measuring mycotoxins in urine and airborne samples. A multi-class mycotoxin method was developed in urine for the determination of aflatoxin B1, aflatoxin M1, ochratoxin A, ochratoxin α, deoxynivalenol, zearalenone, α-zearalenol, ß-zearalenol, fumonisin B1, HT2-toxin and T2-toxin. Analysis was based on liquid chromatography-high resolution mass spectrometry. Sample pre-treatments included enzymatic digestion and an online or offline sample clean-up step. The method was validated according to the European Medicines Agency guidance procedures. In order to estimate external exposure, air samples collected with a CIP 10 (Capteur Individuel de Particules 10) personal dust sampler were analyzed for the quantification of up to ten mycotoxins, including aflatoxins, ochratoxin A, deoxynivalenol, zearalenone, fumonisin B1 and HT-2 toxin and T-2 toxin. The method was validated according to standards for workplace exposure to chemical and biological agents EN 482. Both methods, biomonitoring and airborne mycotoxin measurement, showed good analytical performances. They were successfully applied in a small pilot study to assess mycotoxin contamination in workers during cleaning of a grain elevator. We demonstrated that this approach was suitable for investigating occupational exposure to mycotoxins.

Towards a systematic use of effect biomarkers in population and occupational biomonitoring.

Effect biomarkers can be used to elucidate relationships between exposure to environmental chemicals and their mixtures with associated health outcomes, but they are often underused, as underlying biological mechanisms are not understood. We aim to provide an overview of available effect biomarkers for monitoring chemical exposures in the general and occupational populations, and highlight their potential in monitoring humans exposed to chemical mixtures. We also discuss the role of the adverse outcome pathway (AOP) framework and physiologically based kinetic and dynamic (PBK/D) modelling to strengthen the understanding of the biological mechanism of effect biomarkers, and in particular for use in regulatory risk assessments. An interdisciplinary network of experts from the European chapter of the International Society for Exposure Science (ISES Europe) and the Organization for Economic Co-operation and Development (OECD) Occupational Biomonitoring activity of Working Parties of Hazard and Exposure Assessment group worked together to map the conventional framework of biomarkers and provided recommendations for their systematic use. We summarized the key aspects of this work here, and discussed these in three parts. Part I, we inventory available effect biomarkers and promising new biomarkers for the general population based on the H2020 Human Biomonitoring for Europe (HBM4EU) initiative. Part II, we provide an overview AOP and PBK/D modelling use that improved the selection and interpretation of effect biomarkers. Part III, we describe the collected expertise from the OECD Occupational Biomonitoring subtask effect biomarkers in prioritizing relevant mode of actions (MoAs) and suitable effect biomarkers. Furthermore, we propose a tiered risk assessment approach for occupational biomonitoring. Several effect biomarkers, especially for use in occupational settings, are validated. They offer a direct assessment of the overall health risks associated with exposure to chemicals, chemical mixtures and their transformation products. Promising novel effect biomarkers are emerging for biomonitoring of the general population. Efforts are being dedicated to prioritizing molecular and biochemical effect biomarkers that can provide a causal link in exposure-health outcome associations. This mechanistic approach has great potential in improving human health risk assessment. New techniques such as in silico methods (e.g. QSAR, PBK/D modelling) as well as 'omics data will aid this process. Our multidisciplinary review represents a starting point for enhancing the identification of effect biomarkers and their mechanistic pathways following the AOP framework. This may help in prioritizing the effect biomarker implementation as well as defining threshold limits for chemical mixtures in a more structured way. Several ex vivo biomarkers have been proposed to evaluate combined effects including genotoxicity and xeno-estrogenicity. There is a regulatory need to derive effect-based trigger values using the increasing mechanistic knowledge coming from the AOP framework to address adverse health effects due to exposure to chemical mixtures. Such a mechanistic strategy would reduce the fragmentation observed in different regulations. It could also stimulate a harmonized use of effect biomarkers in a more comparable way, in particular for risk assessments to chemical mixtures.

Biomonitoring of occupational exposure to phthalates: A systematic review.

INTRODUCTION: Phthalates, a group of ubiquitous industrial chemicals, have been widely used in occupational settings, mainly as plasticizers in a variety of applications. Occupational exposure to different phthalates has been studied in several occupational settings using human biomonitoring (HBM). AIM: To provide a comprehensive review of the available literature on occupational exposure to phthalates assessed using HBM and to determine future data needs on the topic as part of the HBM4EU project. METHODS: A systematic search was carried out in the databases of Pubmed, Scopus, and Web of Science for articles published between 2000 and September 4, 2019 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 22 studies on the occupational HBM of phthalates was considered suitable for review. RESULTS AND DISCUSSION: Among the reviewed studies, 19 (86%) focused on DEHP, an old phthalate that is now subject to authorization and planned to be restricted in the EU. Concentrations of MEHHP, one of its metabolites, varied up to 13-fold between studies and across sectors when comparing extreme geometric means, ranging from 11.6 (similar to the general populations) to 151 µg/g creatinine. Only 2 studies focused on newer phthalates such as DiNP and DPHP. Concerning the geographical distribution, 10 studies were performed in Europe (including 6 in Slovakia), 8 in Asia, and 4 in North America, but this distribution is not a good reflection of phthalate production and usage levels worldwide. Most HBM studies were performed in the context of PVC product manufacturing. Future studies should focus on: i) a more uniform approach to sampling timing to facilitate comparisons between studies; ii) newer phthalates; and iii) old phthalates in waste management or recycling. CONCLUSION: Our findings highlight the lack of recent occupational HBM studies on both old and new phthalate exposure in European countries and the need for a harmonized approach. Considering the important policy actions taken in Europe regarding phthalates, it seems relevant to evaluate the impact of these actions on exposure levels and health risks for workers.