usefulness of measurement of blood chromium levels in the assessment of occupational Cr(VI) exposure

Funding Information: This work has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 733032 and received co-funding from the author's organizations and/or Ministries. Luxembourg entered the study at a later stage and thus financed the study at its own means. Publisher Copyright: © 2022 The AuthorsOccupational 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.publishersversionpublishe

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.Highlights: - Suitability of blood biomarkers was evaluated to assess occupational Cr(VI)exposure; - Bath platers and painters had higher Red Blood Cells-Cr levels compared to controls; - Bath platers, painters and welders had higher plasma-Cr levels compared to controls; Red Blood Cells- and Plasma-Cr were highly correlated with inhalable Cr(VI) in platers; Blood-Cr biomarkers can provide information on systemic and intracellular availability.This work has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 733032 and received co-funding from the author’s organizations and/or Ministries. Luxembourg entered the study at a later stage and thus financed the study at its own means.info:eu-repo/semantics/publishedVersio

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 concerns 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 an air level of 5 µg/m3 corresponds to a U-Cr level of 7 µg/g of creatinine. In welders, the same inhalation exposure resulted in lower U-Cr levels reflecting toxicokinetic differences of different chromium species.info:eu-repo/semantics/publishedVersio

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.Highlights: Potential policy impact of the HBM4EU chromates study is presented and discussed; Surveyed policy makers confirmed policy relevance of biomonitoring results; Study considered to support national enforcement and further lowering of OELs; Added value of HBM in the management of occupational exposure to Cr(VI) was demonstrated; Close co-operation with regulators to support policy uptake is emphasised.Funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 733032 and received co-funding from the author's organizations and/or Ministries.info:eu-repo/semantics/publishedVersio

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

Funding Information: The recently completed EU human biomonitoring initiative (HBM4EU, www.hbm4eu.eu/about-hbm4eu/), was a European Joint Programme that aimed to harmonise the collection and use of biomonitoring data to better understand human exposure to chemicals in the environment, in occupational settings and through the use of consumer products to improve chemical risk assessment and management efforts, and to support policy making (Ganzleben et al., 2017). Within the context of the HBM4EU project several priority substances were selected for investigation based on the most important needs of policy makers and risk assessors, as well as common needs of participating countries and a broad range of other stakeholders including trade unions (Ougier et al., 2021). Many of the priority substances, along with having an important economic role, also pose health risks for workers due to their occupational use. One of the priority substances was hexavalent chromium (Cr(VI)), which was the main focus of the first of a series of three different HBM4EU occupational studies (Santonen et al. 2019a, 2022), the other two being focussed on electronic waste (E-waste) and diisocyanates exposures (Jones et al., 2022; Scheepers et al., 2021). In addition to Cr(VI), it was recognised that in chrome plating activities there may also be exposure to another group of HBM4EU priority chemicals, per- and polyfluoroalkyl substances (PFASs). PFASs, including PFOS (perfluorooctane sulfonate), have been used as mist suppressants in chrome plating baths to prevent the evaporation of Cr(VI) vapours (Blepp et al., 2017; Gluge et al., 2020). Although PFOS has now been largely replaced in the EU, many of its substitutes in chrome plating activities are also PFASs which may cause similar health and environmental concerns.Occupational exposure to Cr(VI) has been associated with an increased risk of lung and sinonasal cancers and is suspected to lead to gastrointestinal tract cancers (den Braver-Sewradj et al., 2021; ECHA 2013; IARC 2012). In addition, it is a common cause of occupational asthma, allergic dermatitis and there is a concern for adverse effects on reproductive health (Sun and Costa 2022). Exposure to Cr(VI) may occur in several occupational activities, e.g., in welding, Cr(VI) electroplating and other surface treatment processes such as paint application and removal of old paint containing Cr(VI) (SCOEL 2017). In order to limit the workers’ exposure to Cr(VI) in the EU, Cr(VI) is currently regulated under both the European regulation (EC 1907/2006) on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) and the EU Directive 2004/37/EC on the protection of workers from the risks related to exposure to carcinogens, mutagens or reprotoxic substances at work (CMRD) (EU 2004). The current binding Occupational Exposure Limit (OEL) set under the EU Directive 2004/37/EC is 10 μg/m3 (8-h time-weighted average (8-h TWA)) until January 17, 2025. After that period, the OEL (8-h TWA) will be reduced to 5 μg/m3. For welding, plasma-cutting processes and similar work processes that generate fumes, there is a derogation with an OEL of 25 μg/m³ (8-h TWA) until January 2025; after that date the OEL (8-h TWA) of 5 μg/m3 will be applicable. France, the Netherlands and Denmark already have stricter limits, with an OEL of 1 μg/m3 (8-h TWA) for Cr(VI) in all uses (Beskæftigelsesministeriet 2020; Ministère du travail, 2012; MinSZW 2016). In the US, the American Conference of Governmental Industrial Hygienists (ACGIH) has published, for inhalable Cr(VI) compounds, a threshold limit value (TLV) of 0.2 μg/m3 (8-h TWA) and a TLV Short-Term Exposure Limit (STEL) of 0.5 μg/m3 (ACGIH 2021). No EU-wide biological limit values (BLVs) for Cr(VI) are available, however some Member States have set BLVs for occupational exposure to Cr(VI), measured as urinary chromium (U–Cr). For example, France and Finland have derived BLVs of 2.5 μg/L and 10 μg/L corresponding to their respective OELs of 1 μg/m3 and 5 μg/m3 for Cr(VI) (ANSES 2017; STM 2020). The German Research Foundation (DFG 2020) has established biological exposure equivalents for carcinogenic substances (EKA values), ranging from 12 to 40 μg/L for U–Cr. These correspond to exposures ranging between 30 and 100 μg/m3 soluble alkaline chromate and/or Cr(VI) containing welding fumes over an 8-h work shift (Bolt and Lewalter 2012). Since these current national BLVs are mainly based on studies from plating workers, they include uncertainties especially concerning their applicability to workplaces other than the electroplating industry. One of the main aims of the HBM4EU chromates study was to provide EU relevant data on the current occupational Cr(VI) exposure to support the regulatory risk assessment and decision-making process. In addition, exposure to PFASs was evaluated in a subset of workers performing chrome plating activities.This project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 733032 and received co-funding from the author's organizations and/or Ministries. The project team would like to thank all the companies and workers who participated in the HBM4EU chromates study and all the experts who have contributed to the conduct of the study. Participants of the HBM4EU chromates study workshop and policy questionnaires are also acknowledged. Mr. Jouko Remes and Dr. Kia Gluschkoff (Finnish Institute of Occupational Health) are acknowledged for their assistance with the statistical analyses and figures. Funding Information: This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 733032 and received co-funding from the author's organizations and/or Ministries. Publisher Copyright: © 2022 The AuthorsWithin 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.publishersversionepub_ahead_of_prin

Stress granules regulate stress-induced paraspeckle assembly

Eukaryotic cells contain a variety of RNA-protein macrocomplexes termed RNP granules. Different types of granules share multiple protein components; however, the crosstalk between spatially separated granules remains unaddressed. Paraspeckles and stress granules (SGs) are prototypical RNP granules localized exclusively in the nucleus and cytoplasm, respectively. Both granules are implicated in human diseases, such as amyotrophic lateral sclerosis. We characterized the composition of affinity-purified paraspeckle-like structures and found a significant overlap between the proteomes of paraspeckles and SGs. We further show that paraspeckle hyperassembly is typical for cells subjected to SG-inducing stresses. Using chemical and genetic disruption of SGs, we demonstrate that formation of microscopically visible SGs is required to trigger and maintain stress-induced paraspeckle assembly. Mechanistically, SGs may sequester negative regulators of paraspeckle formation, such as UBAP2L, alleviating their inhibitory effect on paraspeckles. Our study reveals a novel function for SGs as positive regulators of nuclear RNP granule assembly and suggests a role for disturbed SG-paraspeckle crosstalk in human disease

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.This work has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 733032 and received co-funding from the author's organizations and/or Ministries. Luxembourg entered the study at a later stage and thus financed the study at its own means.S

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

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 , 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 expo-sure to chemicals