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- Assessment of occupational exposure to hexavalent chromium – recommendations from HBM4EU chromate studyPublication . Santonen, Tiina; Bocca, Beatrice; Bousoumah, Radia; Duca, Radu Corneliu; Galea, Karen S.; Godderis, Lode; Göen, Thomas; Hardy, Emilie; Iavicoli, Ivo; Janasik, Beata; Jones, Kate; Leese, Elizabeth; Leso, Veruscka; Louro, Henriqueta; Majery, Nicole; Ndaw, Sophie; Pinhal, Hermínia; Porras, Simo P.; Scheepers, Paul T.J.; Sepai, Ovnair; Silva, Maria João; van Nieuwenhuyse, An; Verdonck, Jelle; Viegas, Susana; Wasowicz, WojciechIntroduction: Hexavalent chromium (Cr(VI)) is an important occupational carcinogen. In addition to air monitoring biomonitoring is commonly applied to monitor exposure to Cr(VI). Within the EU biomonitoring initiative, HBM4EU, we explored the applicability of different biomonitoring methods in the assessment of occupational exposure to Cr(VI) in welding and surface treatment activities. Materials and Methods: A multi-center cross-sectional study was performed in Belgium, Finland, France, Italy, Poland, Portugal, the Netherlands, Luxembourg and United Kingdom. Harmonized procedures were used to collect biological and industrial hygiene samples. Contextual information was collected using questionnaires. Altogether 602 exposed workers and controls were included in the study. Exposure biomarkers studied included urinary, red blood cell (RBC) and plasma Cr, and exhaled breath condensate (EBC) Cr(VI)/Cr(III). In addition, number of effect biomarkers were studied. Results: All exposure markers showed highest exposure levels among chrome plating workers. U-Cr showed a good correlation with air Cr(VI) in bath platers and welders. Observed low correlations between different exposure biomarkers suggest that these approaches are not interchangeable but rather complementary. Conclusions: U-Cr showed its value as the first approach for the assessment of internal exposure to Cr(VI). We recommend pre- and post-shift samples for low exposure levels. RBC/P-Cr and EBC-Cr(VI)/Cr(III) provide additional information when more specific information on exposure is needed. The current exposure levels require analytical methods with high sensitivity.
- Biomarkers of effect as determined in human biomonitoring studies on hexavalent chromium and cadmium in the period 2008-2020Publication . Ventura, Célia; Gomes, BC; Oberemm, Axel; Louro, Henriqueta; Huuskonen, Pasi; Mustieles, Vicente; Fernández, Mariana F.; Ndaw, Sophie; Mengelers, Marcel; Luijten, Mirjam; Gundacker, Claudia; Silva, Maria JoãoA 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, β-2-microglobulin (B2-MG) and N-acetyl-β-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.
- Caracterização de biomarcadores de genotoxicidade em trabalhadores expostos a crómio hexavalente: um estudo no âmbito da Iniciativa Europeia em Biomonitorização HumanaPublication . Tavares, Ana; Aimonen, Kukka; Ndaw, Sophie; Fučić, Aleksandra; Catalán, Julia; Duca, Radu Corneliu; Godderis, Lode; Gomes, Bruno C.; Janasik, Beata; Ladeira, Carina; Louro, Henriqueta; Namorado, Sónia; Van Nieuwenhuyse, An; Norppa, Hannu; Scheepers, Paul T.J.; Ventura, Célia; Verdonck, Jelle; Viegas, Susana; Wasowicz, Wojciech; Santonen, Tiina; Silva, Maria JoãoNo 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.
- HBM4EU Chromates Study - Genotoxicity and Oxidative Stress Biomarkers in Workers Exposed to Hexavalent ChromiumPublication . Tavares, Ana; Aimonen, Kukka; Ndaw, Sophie; Fučić, Aleksandra; Catalán, Julia; Duca, Radu Corneliu; Godderis, Lode; Gomes, Bruno C.; Janasik, Beata; Ladeira, Carina; Louro, Henriqueta; Namorado, Sónia; Nieuwenhuyse, An Van; Norppa, Hannu; Scheepers, Paul; Ventura, Célia; Verdonck, Jelle; Viegas, Susana; Wasowicz, Wojciech; Santonen, Tiina; Silva, M.J.; on behalf of the HBM4EU Chromates Study TeamA 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 chromates study - Overall results and recommendations for the biomonitoring of occupational exposure to hexavalent chromiumPublication . Santonen, Tiina; Porras, Simo P.; Bocca, Beatrice; Bousoumah, Radia; Duca, Radu Corneliu; Galea, Karen S.; Godderis, Lode; Göen, Thomas; Hardy, Emilie; Iavicoli, Ivo; Janasik, Beata; Jones, Kate; Leese, Elizabeth; Leso, Veruscka; Louro, Henriqueta; Majery, Nicole; Ndaw, Sophie; Pinhal, Hermínia; Ruggieri, Flavia; Silva, Maria João; van Nieuwenhuyse, An; Verdonck, Jelle; Viegas, Susana; Wasowicz, Wojciech; Sepai, Ovnair; Scheepers, Paul T.J.; Aimonen, Kukka; Antoine, Guillaume; Anzion, Rob; Burgart, Manuella; Castaño, Argelia; Cattaneo, Andrea; Cavallo, Domenico Maria; De Palma, Giuseppe; Denis, Flavien; Gambelunghe, Angela; Gomes, Bruno; Hanser, Ogier; Helenius, Riikka; Ladeira, Carina; López, Marta Esteban; Lovreglio, Piero; Marsan, Philippe; Melczer, Mathieu; Nogueira, Ana; Pletea, Elisabeta; Poels, Katrien; Remes, Jouko; Ribeiro, Edna; Santos, Sílvia Reis; Schaefers, Françoise; Spankie, Sally; Spoek, Robert; Rizki, Mohamed; Rousset, Davy; van Dael, Maurice; Veijalainen, Henna; HBM4EU chromates study teamExposure 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 chromates study - Reflection and lessons learnt from designing and undertaking a collaborative European biomonitoring study on occupational exposure to hexavalent chromiumPublication . Galea, Karen S.; Porras, Simo P.; Viegas, Susana; Bocca, Beatrice; Bousoumah, Radia; Duca, Radu Corneliu; Godderis, Lode; Iavicoli, Ivo; Janasik, Beata; Jones, Kate; Knudsen, Lisbeth E.; Leese, Elizabeth; Leso, Veruscka; Louro, Henriqueta; Ndaw, Sophie; Ruggieri, Flavia; Sepai, Ovnair; Scheepers, Paul T.J.; Silva, Maria J.; Wasowicz, Wojciech; Santonen, TiinaThe 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.
- HBM4EU chromates study - Usefulness of measurement of blood chromium levels in the assessment of occupational Cr(VI) exposurePublication . Ndaw, Sophie; Leso, Veruscka; Bousoumah, Radia; Rémy, Aurélie; Bocca, Beatrice; Duca, Radu Corneliu; Godderis, Lode; Hardy, Emilie; Janasik, Beata; van Nieuwenhuyse, An; Pinhal, Hermínia; Poels, Katrien; Porras, Simo P.; Ruggieri, Flavia; Santonen, Tiina; Santos, Sílvia Reis; Scheepers, Paul T.J.; Silva, Maria João; Verdonck, Jelle; Viegas, Susana; Wasowicz, Wojciech; Iavicoli, Ivo; HBM4EU Chromates Study TeamOccupational 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 infor-mation 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.
- HBM4EU Chromates Study: Determinants of Exposure to Hexavalent Chromium in Plating, Welding and Other Occupational SettingsPublication . Viegas, Susana; Martins, Carla; Bocca, Beatrice; Bousoumah, Radia; Duca, Radu Corneliu; Galea, Karen S.; Godderis, Lode; Iavicoli, Ivo; Janasik, Beata; Jones, Kate; Leese, Elizabeth; Leso, Veruscka; Ndaw, Sophie; van Nieuwenhuyse, An; Poels, Katrien; Porras, Simo P.; Ruggieri, Flavia; Silva, Maria João; Verdonck, Jelle; Wasowicz, Wojciech; Scheepers, Paul T.J.; Santonen, Tiina; HBM4EU Chromates Study TeamWork-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 Diisocyanates Study-Research Protocol for a Collaborative European Human Biological Monitoring Study on Occupational ExposurePublication . Jones, Kate; Galea, Karen S.; Scholten, Bernice; Loikala, Marika; Porras, Simo P.; Bousoumah, Radia; Ndaw, Sophie; Leese, Elizabeth; Louro, Henriqueta; Silva, Maria João; Viegas, Susana; Godderis, Lode; Verdonck, Jelle; Poels, Katrien; Gӧen, Thomas; Duca, Radu-Corneliu; Santonen, Tiina; HBM4EU Diisocyanates Study TeamDiisocyanates 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 assessoccupational 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 hygienemeasurements (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 Occupational Biomonitoring Study on e-Waste-Study ProtocolPublication . Scheepers, Paul T.J.; Duca, Radu Corneliu; Galea, Karen S.; Godderis, Lode; Hardy, Emilie; Knudsen, Lisbeth E.; Leese, Elizabeth; Louro, Henriqueta; Mahiout, Selma; Ndaw, Sophie; Poels, Katrien; Porras, Simo P.; Silva, Maria João; Tavares, Ana Maria; Verdonck, Jelle; Viegas, Susana; Santonen, Tiina; HBM4EU e-Waste Study TeamWorkers 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.