Background: Antimony (Sb) trioxide and antimony trisulfide are “2B: Possibly carcinogenic to humans” and “3: Unclassifiable” according to the International Agency for Research on Cancer (IARC). The U.S. National Toxicology Program (NTP) concluded that antimony trioxide “is reasonably anticipated to be a human carcinogen based on studies in rats and mice”. We investigated the cancer hazard of antimony compounds for workers, a population with high exposure to antimony substances. Methods: Using the “Guidelines for performing systematic reviews in the development of toxicity factors” (Texas Commission on Environmental Quality (TCEQ) 2017) as a guidance, we established a human and an animal toxicology data stream in Medline and ToxLine. Data from this review were applied in a human health risk assessment. Results: A final pool of 10 occupational and 13 animal toxicology articles resulted after application of TCEQ guidelines. Conclusions: Antimony carcinogenicity evidence involving workers is inadequate, based on confounding, small sample sizes, incomparability across studies, and inadequate reference populations. An increased lung cancer risk cannot be excluded. Evidence for lung neoplasms caused by antimony trioxide inhalation in experimental animals is sufficient. Overall, carcinogenicity in workers is probable (International Agency for Research on Cancer (IARC) 2A). It remains unclear from what occupational exposure duration and dose this effect arises and whether exposure threshold values should be reconsidered.

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.

Disease relapse and therapy resistance remain key challenges in treating multiple myeloma. Underlying (epi-)mutational events can promote myelomagenesis and contribute to multi-drug and apoptosis resistance. Therefore, compounds inducing ferroptosis, a form of iron and lipid peroxidation-regulated cell death, are appealing alternative treatment strategies for multiple myeloma and other malignancies. Both ferroptosis and the epigenetic machinery are heavily influenced by oxidative stress and iron metabolism changes. Yet, only a limited number of epigenetic enzymes and modifications have been identified as ferroptosis regulators. In this study, we found that MM1 multiple myeloma cells are sensitive to ferroptosis induction and epigenetic reprogramming by RSL3, irrespective of their glucocorticoid-sensitivity status. LC-MS/MS analysis revealed the formation of non-heme iron-histone complexes and altered expression of histone modifications associated with DNA repair and cellular senescence. In line with this observation, EPIC BeadChip measurements of significant DNA methylation changes in ferroptotic myeloma cells demonstrated an enrichment of CpG probes located in genes associated with cell cycle progression and senescence, such as Nuclear Receptor Subfamily 4 Group A member 2 (NR4A2). Overall, our data show that ferroptotic cell death is associated with an epigenomic stress response that might advance the therapeutic applicability of ferroptotic compounds.

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.

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.