The European Registered Toxicologist (ERT) : Current status and prospects for advancement

Acknowledgements We would like to thank the participants of the five workshops in which the issues presented in this paper were discussed and the revised guidelines prepared, as well as the EUROTOX Executive Committee and the societies of toxicology of Sweden, the Netherlands, Switzerland, Austria and France for their support which allowed the workshops to take place.Peer reviewedPostprin

an ISES Europe statement

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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.publishersversionpublishe

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

Multicenter StudyThe 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.Highlights: Feasibility of conducting harmonised Pan-European biomonitoring study on occupational exposure demonstrated; Developing a successful network and implementation of systematic methodology takes significant dedication from all involved; Methodological improvements were identified which will benefit future large-scale occupational biomonitoring campaigns; Developed multicentre network allows and promotes further opportunities for future research, knowledge sharing and collaboration; Data produced supports science to policy interface in the scope of REACH and occupational safety and health regulations.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 733032 and received co-funding from the author’s organizations and/or Ministries.info:eu-repo/semantics/publishedVersio

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

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

Pesticide residues with hazard classifications relevant to non-target species including humans are omnipresent in the environment and farmer residences

Intensive and widespread use of pesticides raises serious environmental and human health concerns. The presence and levels of 209 pesticide residues (active substances and transformation products) in 625 environmental samples (201 soil, 193 crop, 20 outdoor air, 115 indoor dust, 58 surface water, and 38 sediment samples) have been studied. The samples were collected during the 2021 growing season, across 10 study sites, covering the main European crops, and conventional and organic farming systems. We profiled the pesticide residues found in the different matrices using existing hazard classifications towards non-target organisms and humans. Combining monitoring data and hazard information, we developed an indicator for the prioritization of pesticides, which can support policy decisions and sustainable pesticide use transitions. Eighty-six percent of the samples had at least one residue above the respective limit of detection. One hundred residues were found in soil, 112 in water, 99 in sediments, 78 in crops, 76 in outdoor air, and 197 in indoor dust. The number, levels, and profile of residues varied between farming systems. Our results show that non-approved compounds still represent a significant part of environmental cocktails and should be accounted for in monitoring programs and risk assessments. The hazard profiles analysis confirms the dominance of compounds of low-moderate hazard and underscores the high hazard of some approved compounds and recurring “no data available” situations. Overall, our results support the idea that risk should be assessed in a mixture context, taking environmentally relevant mixtures into consideration. We have uncovered uncertainties and data gaps that should be addressed, as well as the policy implications at the EU approval status level. Our newly introduced indicator can help identify research priority areas, and act as a reference for targeted scenarios set forth in the Farm to Fork pesticide reduction goals

Genotoxicity biomarkers in workers exposed to hexavalent chromium: a study under the European Human Biomonitoring Initiative

No âmbito da Iniciativa Europeia em Biomonitorização Humana (HBM4EU) realizou-se um estudo ocupacional, envolvendo trabalhadores com potencial exposição a crómio hexavalente [Cr( VI)], um reconhecido agente carcinogénico. No presente estudo são apresentados os resultados de biomarcadores de genotoxicidade, incluindo a análise de lesão no DNA e de alterações cromossómicas em células sanguíneas. O estudo foi realizado em vários Países Europeus e abrangeu trabalhadores de diversos setores industriais e atividades, bem como um grupo de controlo constituído por trabalhadores administrativos das mesmas empresas (controlo interno) e de outras não relacionadas com produção/aplicação de Cr( VI) (controlo externo). Os resultados mostraram níveis de alterações cromossómicas (ensaio do micronúcleo) e de lesão no DNA (ensaio do cometa) significativamente aumentados nos trabalhadores expostos comparativamente aos controlos externos ( p=0,03; p<0,001, respetivamente). Estes resultados sugerem que mesmo um baixo nível de exposição ao Cr( VI) representa um risco acrescido para a saúde dos trabalhadores e, principalmente, para os que realizam cromagem em banho. O grupo controlo interno apresentou níveis médios de lesões no DNA e nos cromossomas comparáveis aos do grupo exposto, salientando a relevância de se considerarem também em risco. O uso de biomarcadores de efeito demonstrou ser crucial para a deteção precoce de efeitos biológicos decorrentes de baixos níveis de exposição ao Cr( VI), contribuindo para a identificação de subgrupos em maior risco. O presente estudo vem apoiar a necessidade de uma reavaliação do limite de exposição ocupacional a Cr( VI), bem como da implementação de medidas de gestão de risco conducentes a uma melhor proteção da saúde dos trabalhadores.An occupational study was carried out within the scope of the European Initiative on Human Biomonitoring (HBM4EU), involving workers with potential exposure to hexavalent chromium [Cr(VI)], a recognized carcinogenic agent. In the present study, the results of biomarkers of genotoxicity are presented, including the analysis of DNA damage and chromosomal alterations in blood cells. The study was carried out in several countries and included workers from different industrial sectors and activities, as well as a control group including administrative workers from the same companies (internal control) and from others not related to the production/application of Cr(VI) (external control). Results showed significantly increased levels of chromosomal alterations (micronucleus assay) and DNA damage (comet assay) in exposed workers compared to external controls (p=0.03; p<0.001, respectively). These results suggest that even a low level of exposure to Cr(VI) represents an increased risk for the health of workers and, mainly, for those who per form chromium bath plating. The internal control group displayed DNA and chromosomal damage levels comparable to those of the exposed group, highlighting the impor tance of also being considered as potentially at risk. The use of ef fect biomarkers proved to be crucial for the early detection of biological ef fects resulting from low levels of exposure to Cr(VI), contributing to the identification of subgroups at a higher risk. The present study suppor ts the need for a reassessment of the occupational exposure limit to Cr(VI), as well as the implementation of risk management measures leading to a better protection of workers' health.Este projeto recebeu financiamento do programa de investigação e inovação Horizonte 2020 da União Europeia sob o acordo de subvenção n.º 733032 e recebeu cofinanciamento das organizações dos autores.info:eu-repo/semantics/publishedVersio