Safety and efficacy of a feed additive consisting of 6-phytase produced by Aspergillus oryzae DSM 33737 (HiPhorius™) for all poultry, all Suidae and all fin fish (DSM Nutritional Products Ltd).

Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of 6-phytase produced by the genetically modified strain Aspergillus oryzae DSM 33737 (HiPhorius™ 10, 40, 20L and 50L) as a zootechnical feed additive for all poultry, all Suidae and all fin fish. The FEEDAP Panel concluded that the genetic modification of the production strain does not give rise to safety concerns. Based on the no observed adverse effect level identified in a subchronic oral toxicity study in rats, the additive was considered safe for all poultry, all Suidae and all fin fish at the proposed conditions of use. The Panel also concluded that the use of the product as a feed additive is of no concern for the consumers and the environment. The liquid formulations of the additive are not skin or eye irritants. The two solid ones are not skin irritants but are eye irritants. Owing to the lack of data, the Panel cannot conclude on the skin sensitisation of the final formulations of the additive. Due to the proteinaceous nature of the active substance (6-phytase), the additive is considered a respiratory sensitiser. The Panel concludes that the additive is efficacious when included in the diet of poultry for fattening or reared for laying/breeding, reproductive Suidae, and all fin fish. Due to the lack of sufficient data, the Panel could not conclude on the efficacy for laying and reproductive poultry and growing Suidae.

HBM4EU E-waste study: Assessing persistent organic pollutants in blood, silicone wristbands, and settled dust among E-waste recycling workers in Europe.

E-waste recycling is an increasingly important activity that contributes to reducing the burden of end-of-life electronic and electrical apparatus and allows for the EU's transition to a circular economy. This study investigated the exposure levels of selected persistent organic pollutants (POPs) in workers from e-waste recycling facilities across Europe. The concentrations of seven polychlorinated biphenyls (PCBs) and eight polybrominated diphenyl ethers (PBDEs) congeners were measured by GC-MS. Workers were categorized into five groups based on the type of e-waste handled and two control groups. Generalized linear models were used to assess the determinants of exposure levels among workers. POPs levels were also assessed in dust and silicone wristbands (SWB) and compared with serum. Four PCB congeners (CB 118, 138, 153, and 180) were frequently detected in serum regardless of worker's category. With the exception of CB 118, all tested PCBs were significantly higher in workers compared to the control group. Controls working in the same company as occupationally exposed (Within control group), also displayed higher levels of serum CB 180 than non-industrial controls with no known exposures to these chemicals (Outwith controls) (p < 0.05). BDE 209 was the most prevalent POP in settled dust (16 µg/g) and SWB (220 ng/WB). Spearman correlation revealed moderate to strong positive correlations between SWB and dust. Increased age and the number of years smoked cigarettes were key determinants for workers exposure. Estimated daily intake through dust ingestion revealed that ΣPCB was higher for both the 50th (0.03 ng/kg bw/day) and 95th (0.09 ng/kg bw/day) percentile exposure scenarios compared to values reported for the general population. This study is one of the first to address the occupational exposure to PCBs and PBDEs in Europe among e-waste workers through biomonitoring combined with analysis of settled dust and SWB. Our findings suggest that e-waste workers may face elevated PCB exposure and that appropriate exposure assessments are needed to establish effective mitigation strategies.

Hazard characterization of Alternaria toxins to identify data gaps and improve risk assessment for human health.

Fungi of the genus Alternaria are ubiquitous plant pathogens and saprophytes which are able to grow under varying temperature and moisture conditions as well as on a large range of substrates. A spectrum of structurally diverse secondary metabolites with toxic potential has been identified, but occurrence and relative proportion of the different metabolites in complex mixtures depend on strain, substrate, and growth conditions. This review compiles the available knowledge on hazard identification and characterization of Alternaria toxins. Alternariol (AOH), its monomethylether AME and the perylene quinones altertoxin I (ATX-I), ATX-II, ATX-III, alterperylenol (ALP), and stemphyltoxin III (STTX-III) showed in vitro genotoxic and mutagenic properties. Of all identified Alternaria toxins, the epoxide-bearing analogs ATX-II, ATX-III, and STTX-III show the highest cytotoxic, genotoxic, and mutagenic potential in vitro. Under hormone-sensitive conditions, AOH and AME act as moderate xenoestrogens, but in silico modeling predicts further Alternaria toxins as potential estrogenic factors. Recent studies indicate also an immunosuppressive role of AOH and ATX-II; however, no data are available for the majority of Alternaria toxins. Overall, hazard characterization of Alternaria toxins focused, so far, primarily on the commercially available dibenzo-α-pyrones AOH and AME and tenuazonic acid (TeA). Limited data sets are available for altersetin (ALS), altenuene (ALT), and tentoxin (TEN). The occurrence and toxicological relevance of perylene quinone-based Alternaria toxins still remain to be fully elucidated. We identified data gaps on hazard identification and characterization crucial to improve risk assessment of Alternaria mycotoxins for consumers and occupationally exposed workers.

Safety and efficacy of a feed additive consisting of zeolites (≥ 50%) obtained from Neapolitan Yellow Tufa for all animal species (Italiana Zeoliti s.r.l.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of zeolites (≥ 50%) obtained from Neapolitan Yellow Tufa as a technological additive (functional group: anticaking) for all animal species. The additive is specified to contain not less than 50% of zeolites, namely phillipsite, chabazite and analcime. Neapolitan Yellow Tufa originates from the volcanic activity of Campi Flegrei, Italy. According to the conventional risk assessment, due to a lack of adequate data, the safety of the additive for the target species cannot be established. Based on current knowledge, there is no indication of substantial absorption of the components of the additive and, therefore, of concern for the consumer. The additive poses a risk by inhalation. It is not irritant to the skin. The Panel cannot conclude on the eye irritancy and on the dermal and respiratory sensitisation potential of the additive. As no suitable data in line with the requirements of the Guidance on risk assessment of nanomaterials were provided by the applicant, the potential risks associated with the presence of nanoparticles for the target species, the consumer and the user could not be assessed. The additive is safe for the environment. The additive is considered to be efficacious in feedingstuffs for all animal species at 20,000 mg/kg complete feed.

Safety and efficacy of the feed additive Anpro consisting of a mixture of Sepiolite and Kieselguhr (diatomaceous earth) for all terrestrial animal species (Anpario plc).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of the mixture of Sepiolite and Kieselguhr (diatomaceous earth) (Anpro) as a technological feed additive for all terrestrial animal species. According to the conventional risk assessment, due to lack of adequate data, the safety of the additive Anpro for the target species cannot be established. Based on current knowledge, there is no indication of substantial absorption of the components of the additive and therefore no concern for the consumer. The additive poses a risk by inhalation. It is not irritant to the skin or eyes but should be considered as skin sensitiser. As no suitable data in line with the requirements of the Guidance on risk assessment of nanomaterials were provided by the applicant, the potential risks associated with the presence of nanoparticles could not be assessed for the target species, the consumer and the user. The additive is safe for the environment. The FEEDAP Panel is not in the position to conclude on the efficacy of the additive for all terrestrial animal species.

Safety of a feed additive consisting of Duddingtonia flagrans NCIMB 30336 (BioWorma®) for all grazing animals (International Animal Health Products Pty Ltd).

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety of a feed additive consisting of Duddingtonia flagrans NCIMB 30336 (BioWorma®) for all grazing animals. The safety and efficacy of the additive have been already assessed previously, however the FEEDAP Panel could not conclude on the safety of the additive for the target species and the consumers due to the limitations in the dataset provided. For the current assessment, the applicant submitted a new tolerance trial in dairy cows and new toxicological studies. After the assessment of the new data submitted, the FEEDAP Panel concluded that the use of the feed additive in animal nutrition under the conditions of use proposed is of no concern for dairy cows. This conclusion can be extrapolated to all dairy bovines, ovines and caprines, but not to fattening and rearing animals of those species. Due to the lack of data, the FEEDAP Panel cannot conclude on the safety of the additive for other grazing species/categories. The FEEDAP Panel concluded that the additive is safe for the consumers.

Safety and efficacy of a feed additive consisting of endo-1,4-beta-xylanase (produced by Aspergillus oryzae DSM 33700) (RONOZYME® WX (CT/L)) for all poultry species and all Suidae (DSM nutritional products ltd).

The additive RONOZYME® WX (CT/L) contains endo-1,4-beta-xylanase produced with a genetically modified strain of the filamentous fungus Aspergillus oryzae; the additive is currently authorised for poultry for fattening, weaned piglets, pigs for fattening, lactating sows and laying hens. The applicant has requested to change the production strain, substituting strain A. oryzae DSM 26372 with A. oryzae DSM 33700, and to extend the use of the additive to all poultry species and all Suidae. RONOZYME® WX (CT/L), manufactured with the production strain A. oryzae DSM 33700, did not give rise to safety concerns with regard to the genetic modification of the production strain. No viable cells of the production strain nor its DNA were detected in an intermediate product representative of both final formulations of the additive. RONOZYME® WX (CT/L) was considered safe for all poultry species and all Suidae at the recommended inclusion levels. The use of RONOZYME® WX CT and L manufactured with the production strain A. oryzae DSM 33700 raised no concerns for consumers. RONOZYME® WX L is not an eye irritant; however, no conclusions could be drawn on the potential of RONOZYME® WX CT to be an eye irritant. Both formulations are not irritant to the skin, but due to the lack of data, the FEEDAP Panel was not able to conclude on the potential of both formulations of the additive to be skin sensitisers. Due to the proteinaceous nature of the active substance, the additive is considered a respiratory sensitiser. The additive manufactured by A. oryzae DSM 33700 raises no safety concerns for the environment. The additive has the potential to be efficacious in all poultry species and all Suidae at 100 and 200 FXU/kg complete feed, respectively.

Assessing the Genotoxicity of Cellulose Nanomaterials in a Co-Culture of Human Lung Epithelial Cells and Monocyte-Derived Macrophages.

Cellulose micro/nanomaterials (CMNMs) are innovative materials with a wide spectrum of industrial and biomedical applications. Although cellulose has been recognized as a safe material, the unique properties of its nanosized forms have raised concerns about their safety for human health. Genotoxicity is an endpoint that must be assessed to ensure that no carcinogenic risks are associated with exposure to nanomaterials. In this study, we evaluated the genotoxicity of two types of cellulose micro/nanofibrils (CMF and CNF) and one sample of cellulose nanocrystals (CNC), obtained from industrial bleached Eucalyptus globulus kraft pulp. For that, we exposed co-cultures of human alveolar epithelial A549 cells and THP-1 monocyte-derived macrophages to a concentration range of each CMNM and used the micronucleus (MN) and comet assays. Our results showed that only the lowest concentrations of the CMF sample were able to induce DNA strand breaks (FPG-comet assay). However, none of the three CMNMs produced significant chromosomal alterations (MN assay). These findings, together with results from previous in vitro studies using monocultures of A549 cells, indicate that the tested CNF and CNC are not genotoxic under the conditions tested, while the CMF display a low genotoxic potential.

FAIR environmental and health registry (FAIREHR)- supporting the science to policy interface and life science research, development and innovation.

The environmental impact on health is an inevitable by-product of human activity. Environmental health sciences is a multidisciplinary field addressing complex issues on how people are exposed to hazardous chemicals that can potentially affect adversely the health of present and future generations. Exposure sciences and environmental epidemiology are becoming increasingly data-driven and their efficiency and effectiveness can significantly improve by implementing the FAIR (findable, accessible, interoperable, reusable) principles for scientific data management and stewardship. This will enable data integration, interoperability and (re)use while also facilitating the use of new and powerful analytical tools such as artificial intelligence and machine learning in the benefit of public health policy, and research, development and innovation (RDI). Early research planning is critical to ensuring data is FAIR at the outset. This entails a well-informed and planned strategy concerning the identification of appropriate data and metadata to be gathered, along with established procedures for their collection, documentation, and management. Furthermore, suitable approaches must be implemented to evaluate and ensure the quality of the data. Therefore, the 'Europe Regional Chapter of the International Society of Exposure Science' (ISES Europe) human biomonitoring working group (ISES Europe HBM WG) proposes the development of a FAIR Environment and health registry (FAIREHR) (hereafter FAIREHR). FAIR Environment and health registry offers preregistration of studies on exposure sciences and environmental epidemiology using HBM (as a starting point) across all areas of environmental and occupational health globally. The registry is proposed to receive a dedicated web-based interface, to be electronically searchable and to be available to all relevant data providers, users and stakeholders. Planned Human biomonitoring studies would ideally be registered before formal recruitment of study participants. The resulting FAIREHR would contain public records of metadata such as study design, data management, an audit trail of major changes to planned methods, details of when the study will be completed, and links to resulting publications and data repositories when provided by the authors. The FAIREHR would function as an integrated platform designed to cater to the needs of scientists, companies, publishers, and policymakers by providing user-friendly features. The implementation of FAIREHR is expected to yield significant benefits in terms of enabling more effective utilization of human biomonitoring (HBM) data.

How to use human biomonitoring in chemical risk assessment: Methodological aspects, recommendations, and lessons learned from HBM4EU.

One of the aims of the European Human Biomonitoring Initiative, HBM4EU, was to provide examples of and good practices for the effective use of human biomonitoring (HBM) data in human health risk assessment (RA). The need for such information is pressing, as previous research has indicated that regulatory risk assessors generally lack knowledge and experience of the use of HBM data in RA. By recognising this gap in expertise, as well as the added value of incorporating HBM data into RA, this paper aims to support the integration of HBM into regulatory RA. Based on the work of the HBM4EU, we provide examples of different approaches to including HBM in RA and in estimations of the environmental burden of disease (EBoD), the benefits and pitfalls involved, information on the important methodological aspects to consider, and recommendations on how to overcome obstacles. The examples are derived from RAs or EBoD estimations made under the HBM4EU for the following HBM4EU priority substances: acrylamide, o-toluidine of the aniline family, aprotic solvents, arsenic, bisphenols, cadmium, diisocyanates, flame retardants, hexavalent chromium [Cr(VI)], lead, mercury, mixture of per-/poly-fluorinated compounds, mixture of pesticides, mixture of phthalates, mycotoxins, polycyclic aromatic hydrocarbons (PAHs), and the UV-filter benzophenone-3. Although the RA and EBoD work presented here is not intended to have direct regulatory implications, the results can be useful for raising awareness of possibly needed policy actions, as newly generated HBM data from HBM4EU on the current exposure of the EU population has been used in many RAs and EBoD estimations.

Safety and efficacy of a feed additive consisting of endo-1,4-ß-d-mannanase produced by Thermothelomyces thermophilusDSM 33149 (Natupulse® TS/TS L) for chickens and turkeys for fattening, minor poultry species for fattening and ornamental birds (BASF SE).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of endo-1,4-ß-d-mannanase produced by Thermothelomyces thermophilus DSM 33149 (Natupulse® TS/TS L) as a zootechnical feed additive for chickens and turkeys for fattening, minor poultry species for fattening and ornamental birds. The additive under assessment, Natupulse® TS/TS L, does not pose any safety concern regarding the production strain. The FEEDAP Panel concluded that the additive is tolerated by chickens for fattening, and this conclusion can be extrapolated to all poultry for fattening. Due to the lack of reliable data regarding the potential of the additive to induce chromosomal damage, the FEEDAP Panel cannot conclude on the safety of the additive for the target species and on the safety for consumer. The use of the additive in animal nutrition is considered safe for the environment. The additive is considered not to be irritant to the skin and eyes but is considered a respiratory sensitiser, although exposure by inhalation is unlikely. The Panel could not conclude on the potential of the additive to be a skin sensitiser. Due to the lack of reliable data, the FEEDAP Panel considered that a potential of the additive to induce chromosomal damage in exposed unprotected users cannot be excluded. Consequently, exposure of users should be minimised. The Panel concluded that the additive Natupulse® TS/TS L has the potential to be efficacious in chickens for fattening at the proposed conditions of use and this conclusion can be extrapolated to turkeys for fattening, minor poultry species for fattening and ornamental birds.

Implementation of effect biomarkers in human biomonitoring studies: A systematic approach synergizing toxicological and epidemiological knowledge.

Human biomonitoring (HBM) studies have highlighted widespread daily exposure to environmental chemicals. Some of these are suspected to contribute to adverse health outcomes such as reproductive, neurological, and metabolic disorders, among other developmental and chronic impairments. One of the objectives of the H2020 European Human Biomonitoring Initiative (HBM4EU) was the development of informative effect biomarkers for application in a more systematic and harmonized way in large-scale European HBM studies. The inclusion of effect biomarkers would complement exposure data with mechanistically-based information on early and late adverse effects. For this purpose, a stepwise strategy was developed to identify and implement a panel of validated effect biomarkers in European HBM studies. This work offers an overview of the complete procedure followed, from comprehensive literature search strategies, selection of criteria for effect biomarkers and their classification and prioritization, based on toxicological data and adverse outcomes, to pilot studies for their analytical, physiological, and epidemiological validation. We present the example of one study that demonstrated the mediating role of the effect biomarker status of brain-derived neurotrophic factor BDNF in the longitudinal association between infant bisphenol A (BPA) exposure and behavioral function in adolescence. A panel of effect biomarkers has been implemented in the HBM4EU Aligned Studies as main outcomes, including traditional oxidative stress, reproductive, and thyroid hormone biomarkers. Novel biomarkers of effect, such as DNA methylation status of BDNF and kisspeptin (KISS) genes were also evaluated as molecular markers of neurological and reproductive health, respectively. A panel of effect biomarkers has also been applied in HBM4EU occupational studies, such as micronucleus analysis in lymphocytes and reticulocytes, whole blood comet assay, and malondialdehyde, 8-oxo-2'-deoxyguanosine and untargeted metabolomic profile in urine, to investigate, for example, biological changes in response to hexavalent chromium Cr(VI) exposure. The use of effect biomarkers in HBM4EU has demonstrated their ability to detect early biological effects of chemical exposure and to identify subgroups that are at higher risk. The roadmap developed in HBM4EU confirms the utility of effect biomarkers, and support one of the main objectives of HBM research, which is to link exposure biomarkers to mechanistically validated effect and susceptibility biomarkers in order to better understand the public health implications of human exposure to environmental chemicals.

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.

Interpreting biomonitoring data: Introducing the international human biomonitoring (i-HBM) working group's health-based guidance value (HB2GV) dashboard.

Human biomonitoring (HBM) data measured in specific contexts or populations provide information for comparing population exposures. There are numerous health-based biomonitoring guidance values, but to locate these values, interested parties need to seek them out individually from publications, governmental reports, websites and other sources. Until now, there has been no central, international repository for this information. Thus, a tool is needed to help researchers, public health professionals, risk assessors, and regulatory decision makers to quickly locate relevant values on numerous environmental chemicals. A free, on-line repository for international health-based guidance values to facilitate the interpretation of HBM data is now available. The repository is referred to as the "Human Biomonitoring Health-Based Guidance Value (HB2GV) Dashboard". The Dashboard represents the efforts of the International Human Biomonitoring Working Group (i-HBM), affiliated with the International Society of Exposure Science. The i-HBM's mission is to promote the use of population-level HBM data to inform public health decision-making by developing harmonized resources to facilitate the interpretation of HBM data in a health-based context. This paper describes the methods used to compile the human biomonitoring health-based guidance values, how the values can be accessed and used, and caveats with using the Dashboard for interpreting HBM data. To our knowledge, the HB2GV Dashboard is the first open-access, curated database of HBM guidance values developed for use in interpreting HBM data. This new resource can assist global HBM data users such as risk assessors, risk managers and biomonitoring programs with a readily available compilation of guidance values.

Adverse Outcome Pathways Associated with the Ingestion of Titanium Dioxide Nanoparticles-A Systematic Review.

Titanium dioxide nanoparticles (TiO2-NPs) are widely used, and humans are exposed through food (E171), cosmetics (e.g., toothpaste), and pharmaceuticals. The oral and gastrointestinal (GIT) tract are the first contact sites, but it may be systemically distributed. However, a robust adverse outcome pathway (AOP) has not been developed upon GIT exposure to TiO2-NPs. The aim of this review was to provide an integrative analysis of the published data on cellular and molecular mechanisms triggered after the ingestion of TiO2-NPs, proposing plausible AOPs that may drive policy decisions. A systematic review according to Prisma Methodology was performed in three databases of peer-reviewed literature: Pubmed, Scopus, and Web of Science. A total of 787 records were identified, screened in title/abstract, being 185 used for data extraction. The main endpoints identified were oxidative stress, cytotoxicity/apoptosis/cell death, inflammation, cellular and systemic uptake, genotoxicity, and carcinogenicity. From the results, AOPs were proposed where colorectal cancer, liver injury, reproductive toxicity, cardiac and kidney damage, as well as hematological effects stand out as possible adverse outcomes. The recent transgenerational studies also point to concerns with regard to population effects. Overall, the findings further support a limitation of the use of TiO2-NPs in food, announced by the European Food Safety Authority (EFSA).

Toxicological Assessment of Cellulose Nanomaterials: Oral Exposure.

Cellulose nanomaterials (CNMs) have emerged recently as an important group of sustainable bio-based nanomaterials (NMs) with potential applications in multiple sectors, including the food, food packaging, and biomedical fields. The widening of these applications leads to increased human oral exposure to these NMs and, potentially, to adverse health outcomes. Presently, the potential hazards regarding oral exposure to CNMs are insufficiently characterised. There is a need to understand and manage the potential adverse effects that might result from the ingestion of CNMs before products using CNMs reach commercialisation. This work reviews the potential applications of CNMs in the food and biomedical sectors along with the existing toxicological in vitro and in vivo studies, while also identifying current knowledge gaps. Relevant considerations when performing toxicological studies following oral exposure to CNMs are highlighted. An increasing number of studies have been published in the last years, overall showing that ingested CNMs are not toxic to the gastrointestinal tract (GIT), suggestive of the biocompatibility of the majority of the tested CNMs. However, in vitro and in vivo genotoxicity studies, as well as long-term carcinogenic or reproductive toxicity studies, are not yet available. These studies are needed to support a wider use of CNMs in applications that can lead to human oral ingestion, thereby promoting a safe and sustainable-by-design approach.

Developing human biomonitoring as a 21st century toolbox within the European exposure science strategy 2020-2030.

Human biomonitoring (HBM) is a crucial approach for exposure assessment, as emphasised in the European Commission's Chemicals Strategy for Sustainability (CSS). HBM can help to improve chemical policies in five major key areas: (1) assessing internal and aggregate exposure in different target populations; 2) assessing exposure to chemicals across life stages; (3) assessing combined exposure to multiple chemicals (mixtures); (4) bridging regulatory silos on aggregate exposure; and (5) enhancing the effectiveness of risk management measures. In this strategy paper we propose a vision and a strategy for the use of HBM in chemical regulations and public health policy in Europe and beyond. We outline six strategic objectives and a roadmap to further strengthen HBM approaches and increase their implementation in the regulatory risk assessment of chemicals to enhance our understanding of exposure and health impacts, enabling timely and targeted policy interventions and risk management. These strategic objectives are: 1) further development of sampling strategies and sample preparation; 2) further development of chemical-analytical HBM methods; 3) improving harmonisation throughout the HBM research life cycle; 4) further development of quality control / quality assurance throughout the HBM research life cycle; 5) obtain sustained funding and reinforcement by legislation; and 6) extend target-specific communication with scientists, policymakers, citizens and other stakeholders. HBM approaches are essential in risk assessment to address scientific, regulatory and societal challenges. HBM requires full and strong support from the scientific and regulatory domain to reach its full potential in public and occupational health assessment and in regulatory decision-making.

Occupational Exposure to Hexavalent Chromium, Nickel and PAHs: A Mixtures Risk Assessment Approach Based on Literature Exposure Data from European Countries.

Hexavalent chromium (Cr(VI)), nickel (Ni) and polycyclic aromatic hydrocarbons (PAHs) are genotoxic co-occurring lung carcinogens whose occupational health risk is still understudied. This study, conducted within the European Human Biomonitoring Initiative (HBM4EU), aimed at performing a mixtures risk assessment (MRA) based on published human biomonitoring (HBM) data from Cr(VI), Ni and/or PAHs occupational co-exposure in Europe. After data extraction, Risk Quotient (RQ) and Sum of Risk Quotients (SRQ) were calculated for binary and ternary mixtures to characterise the risk. Most selected articles measured urinary levels of Cr and Ni and a SRQ > 1 was obtained for co-exposure levels in welding activities, showing that there is concern regarding co-exposure to these substances. Similarly, co-exposure to mixtures of Cr(VI), Ni and PAHs in waste incineration settings resulted in SRQ > 1. In some studies, a low risk was estimated based on the single substances' exposure level (RQ < 1), but the mixture was considered of concern (SRQ > 1), highlighting the relevance of considering exposure to the mixture rather than to its single components. Overall, this study points out the need of using a MRA based on HBM data as a more realistic approach to assess and manage the risk at the workplace, in order to protect workers' health.

The Use of Human Biomonitoring to Assess Occupational Exposure to PAHs in Europe: A Comprehensive Review.

Polycyclic aromatic hydrocarbons (PAHs) are among the chemicals with proven impact on workers' health. The use of human biomonitoring (HBM) to assess occupational exposure to PAHs has become more common in recent years, but the data generated need an overall view to make them more usable by regulators and policymakers. This comprehensive review, developed under the Human Biomonitoring for Europe (HBM4EU) Initiative, was based on the literature available from 2008-2022, aiming to present and discuss the information on occupational exposure to PAHs, in order to identify the strengths and limitations of exposure and effect biomarkers and the knowledge needs for regulation in the workplace. The most frequently used exposure biomarker is urinary 1-hydroxypyrene (1-OH-PYR), a metabolite of pyrene. As effect biomarkers, those based on the measurement of oxidative stress (urinary 8-oxo-dG adducts) and genotoxicity (blood DNA strand-breaks) are the most common. Overall, a need to advance new harmonized approaches both in data and sample collection and in the use of appropriate biomarkers in occupational studies to obtain reliable and comparable data on PAH exposure in different industrial sectors, was noted. Moreover, the use of effect biomarkers can assist to identify work environments or activities of high risk, thus enabling preventive risk mitigation and management measures.

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.