Assessing the impact of authorisation process as a regulatory tool in the European REACH regulation: A study on improving occupational safety for applying companies.

This study looks into the effectiveness of the authorisation procedure as a regulatory instrument within the framework of the European REACH regulation. It highlights its impact on enhancing occupational safety and health for both applicants and companies utilising the substances. This procedure encompasses manufacturers, importers, and downstream users of substances, as well as representatives of foreign manufacturers who are also eligible to seek authorisation. When applying for authorisation, the ECHA Risk Assessment Committee (RAC) assesses the risks associated with the intended uses of the substance, including the appropriateness and effectiveness of the Occupational Conditions (OCs) and Risk Management Measures (RMMs) described in the application and the risks posed by potential alternatives. If the RAC determines that the OCs/RMMs are inadequate for managing or controlling the risk, or if the measures to protect workers are deemed insufficient, it may recommend additional measures to enhance occupational safety and health or environmental protection. The 398 processed Applications for Authorisation (AfA) that have been submitted to date were examined to determine these recommended measures, categorised as Conditions for use, Monitoring arrangements, and Recommendations for Review Reports. Overall, a significant improvement concerning occupational safety and health seems necessary, as indicated by the large number of measures recommended by the ECHA Committee for Risk Assessment (RAC) and ECHA Committee for Socio-economic Analysis (SEAC) or supplemented by the European Commission. In addition to the proposed measures, a short assessment provided by the committees as to whether the operational conditions and risk management measures are adequate in controlling the risks is also included in the study.

The relevance of oral exposure in the workplace: a systematic review and meta-analysis.

Introduction: The inclusion of all relevant exposure routes in the exposure assessment is essential for the protection of workers. However, under European chemical regulations but also for workplace risk assessments according to occupational safety and health (OSH) requirements, the quantitative assessment of oral exposure is usually neglected assuming good occupational hygiene. In contrast, several studies point to the importance of unintentional ingestion in the workplace. To our knowledge, there is no systematic analysis of the extent of this exposure route. Methods: Therefore, the aim of this study was to assess systematically the current knowledge on the relevance of occupational oral exposure using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) method. Five electronic databases and nine institutional websites were searched for all publications on the relevance. The data were extracted into a concept matrix. In the subsequent meta-analysis, the identified conclusions on the relevance were analyzed. In addition, the measurement methods or modeling approaches that were described for occupational oral exposure were determined as well as the potentially relevant workplaces and substances. Results: In total, 147 studies were included in this analysis that contain a general or several, differentiated assessments of the relevance of occupational oral exposure. Nine of these studies assessed this exposure route as irrelevant. However, 123 studies considered oral exposure as potentially contributing and 80 studies explicitly identified it as relevant. 78 and 94 of the publications described modeling and measurement approaches, respectively. The workplaces frequently identified as potentially or explicitly relevant were other indoor, other industrial or recycling workplaces. Analogously, metals, dust and powders or pesticides were the most frequently investigated substance groups. Discussion: As several studies assessed occupational oral exposure as relevant in the context of different workplaces and substances, further investigation of this exposure route is needed. This systematic review and meta-analysis serve as a basis for further development of feasible assessment methods for this route of exposure.

Inhalation and dermal exposure to biocidal products during foam and spray applications.

OBJECTIVES: Foaming and spraying are common application techniques for biocidal products. In the past, inhalation and dermal exposure during spraying have been investigated extensively. Currently, however, no exposure data are available for foaming, hindering a reliable risk assessment for foam applications of biocidal products. The focus of this project was the quantification of inhalation and potential dermal exposure to non-volatile active substances during the foam application of biocidal products in occupational settings. In some settings, exposure during spray application was measured for comparative purposes. METHODS: The inhalation and dermal exposure of operators were investigated during the application of benzalkonium chlorides and pyrethroids by foaming and spraying, considering both small- and large-scale application devices. Inhalation exposure was measured by personal air sampling; potential dermal exposure was measured using coveralls and gloves. RESULTS: Potential dermal exposure was substantially higher than inhalation exposure. Changing from spraying to foaming reduced inhalation exposure to airborne non-volatile active substances, but had no relevant effect on potential dermal exposure. However, for potential dermal exposure, considerable differences were observed between the application device categories. CONCLUSIONS: To our knowledge, this study presents the first comparative exposure data for the foam and spray application of biocidal products in occupational settings with detailed contextual information. The results indicate a reduction of inhalation exposure with foam application compared to spray application. However, special attention is necessary for dermal exposure, which is not reduced by this intervention.

Aerosol formation during foam application of non-volatile biocidal substances.

The application of biocidal products by foam is considered an alternative to droplet spraying when disinfecting surfaces or fighting infestations. Inhalation exposure to aerosols containing the biocidal substances cannot be ruled out during foaming. In contrast to droplet spraying, very little is known about aerosol source strength during foaming. In this study, the formation of inhalable aerosols was quantified according to the aerosol release fractions of the active substance. The aerosol release fraction is defined as the mass of active substance transferred into inhalable airborne particles during foaming, normalised to the total amount of active substance released through the foam nozzle. Aerosol release fractions were measured in control chamber experiments where common foaming technologies were operated according to their typical conditions of use. These investigations include foams generated mechanically by actively mixing air with a foaming liquid as well as systems that use a blowing agent for foam formation. The values of the aerosol release fraction ranged from 3.4 × 10-6 to 5.7 × 10-3 (average values). For foaming processes based on mixing air and the foaming liquid, the release fractions could be correlated to the process and foam parameters such as foam exit velocity, nozzle dimensions, and foam expansion ratio.

Understanding the limitations and application of occupational exposure models in a REACH context.

Exposure modeling plays a significant role for regulatory organizations, companies, and professionals involved in assessing and managing occupational health risks in workplaces. One context in which occupational exposure models are particularly relevant is the REACH Regulation in the European Union (Regulation (EC) No 1907/2006). This commentary describes the models for the occupational inhalation exposure assessment of chemicals within the REACH framework, their theoretical background, applications, and limitations, as well as the latest developments and priorities for model improvement. Summing up the debate, despite its relevance and importance in the context of REACH not being in question, occupational exposure modeling needs to be improved in many respects. There is a need to reach a wide consensus on several key issues (e.g., the theoretical background and the reliability of modeling tools), to consolidate and monitor model performance and regulatory acceptance, and to align practices and policies regarding exposure modeling.

The European exposure science strategy 2020-2030.

Exposure science is an emerging and rapidly growing field dedicated to all aspects concerning the contact between chemical, biological, physical or psycho-social stressors and human and ecological receptors. With that, exposure science plays a central role in protecting human and ecosystem health, and contributes to the global transition towards a green and sustainable society. In Europe, however, exposure science is currently not sufficiently recognised as a scientific field, resulting in inefficient uptake into policies. In response, the wider European exposure science community developed elements and actions under the auspices of the Europe Regional Chapter of the International Society of Exposure Science (ISES Europe), for identified priority areas, namely education, exposure models, exposure data, human biomonitoring, and policy uptake. In the present document, we synthesize these strategic elements into an overarching 'European Exposure Science Strategy 2020-2030', following three strategic objectives that focus on acknowledging exposure science as an independent and interconnected field, harmonizing approaches and tools across regulations, and exploring collaboration, education and funding mechanisms. To operationalise this strategy, we present concrete key actions and propose initiatives and funding options for advancing the underlying science, cultivating broader education and cross-sector exposure knowledge transfer, and fostering effective uptake of exposure information into policy. We aim at anchoring European efforts in the global exposure science context, with a special focus on the interface between scientific advancements, application in decision support, and dissemination and training. This will help to develop exposure science as a strong scientific field with the ultimate goal to successfully assess and manage various stressors across sectors and geographic scales.

Exposure modelling in Europe: how to pave the road for the future as part of the European Exposure Science Strategy 2020-2030.

Exposure models are essential in almost all relevant contexts for exposure science. To address the numerous challenges and gaps that exist, exposure modelling is one of the priority areas of the European Exposure Science Strategy developed by the European Chapter of the International Society of Exposure Science (ISES Europe). A strategy was developed for the priority area of exposure modelling in Europe with four strategic objectives. These objectives are (1) improvement of models and tools, (2) development of new methodologies and support for understudied fields, (3) improvement of model use and (4) regulatory needs for modelling. In a bottom-up approach, exposure modellers from different European countries and institutions who are active in the fields of occupational, population and environmental exposure science pooled their expertise under the umbrella of the ISES Europe Working Group on exposure models. This working group assessed the state-of-the-art of exposure modelling in Europe by developing an inventory of exposure models used in Europe and reviewing the existing literature on pitfalls for exposure modelling, in order to identify crucial modelling-related strategy elements. Decisive actions were defined for ISES Europe stakeholders, including collecting available models and accompanying information in a living document curated and published by ISES Europe, as well as a long-term goal of developing a best-practices handbook. Alongside these actions, recommendations were developed and addressed to stakeholders outside of ISES Europe. Four strategic objectives were identified with an associated action plan and roadmap for the implementation of the European Exposure Science Strategy for exposure modelling. This strategic plan will foster a common understanding of modelling-related methodology, terminology and future research in Europe, and have a broader impact on strategic considerations globally.

Theoretical Background of Occupational-Exposure Models-Report of an Expert Workshop of the ISES Europe Working Group "Exposure Models".

On 20 October 2020, the Working Group "Exposure Models" of the Europe Regional Chapter of the International Society of Exposure Science (ISES Europe) organised an online workshop to discuss the theoretical background of models for the assessment of occupational exposure to chemicals. In this report, participants of the workshop with an active role before and during the workshop summarise the most relevant discussion points and conclusions of this well-attended workshop. ISES Europe has identified exposure modelling as one priority area for the strategic development of exposure science in Europe in the coming years. This specific workshop aimed to discuss the main challenges in developing, validating, and using occupational-exposure models for regulatory purposes. The theoretical background, application domain, and limitations of different modelling approaches were presented and discussed, focusing on empirical "modifying-factor" or "mass-balance-based" approaches. During the discussions, these approaches were compared and analysed. Possibilities to address the discussed challenges could be a validation study involving alternative modelling approaches. The wider discussion touched upon the close relationship between modelling and monitoring and the need for better linkage of the methods and the need for common monitoring databases that include data on model parameters.

Modelling Exposure by Spraying Activities-Status and Future Needs.

Spray applications enable a uniform distribution of substances on surfaces in a highly efficient manner, and thus can be found at workplaces as well as in consumer environments. A systematic literature review on modelling exposure by spraying activities has been conducted and status and further needs have been discussed with experts at a symposium. This review summarizes the current knowledge about models and their level of conservatism and accuracy. We found that extraction of relevant information on model performance for spraying from published studies and interpretation of model accuracy proved to be challenging, as the studies often accounted for only a small part of potential spray applications. To achieve a better quality of exposure estimates in the future, more systematic evaluation of models is beneficial, taking into account a representative variety of spray equipment and application patterns. Model predictions could be improved by more accurate consideration of variation in spray equipment. Inter-model harmonization with regard to spray input parameters and appropriate grouping of spray exposure situations is recommended. From a user perspective, a platform or database with information on different spraying equipment and techniques and agreed standard parameters for specific spraying scenarios from different regulations may be useful.

Prediction of Dermal Exposure to Chemical Substances Using a Fluorescence Method within the SysDEA Project.

Dermal exposure is an important exposure route for occupational exposure and risk assessment. A fluorescence method has been developed to quantify occupational dermal exposure based on a visualization technique, using Tinopal SWN as a fluorescent tracer. The method was developed within the framework of a large experimental study, the SysDEA project. In SysDEA, dermal exposure was measured with different methods for 10 simulated exposure situations by sampling powder and liquid formulations containing Tinopal SWN on coveralls and patches and subsequently chemically analysing them. For the fluorescence method, photographs of exposed volunteers who performed the experiments were taken inside a room which consisted of an optimized arrangement of several UV irradiating tube light brackets, reflective and non-reflective backgrounds for maximum light diffusion and a camera. Image processing analysis software processed these photographs to obtain corresponding light intensity in terms of summed pixel values. To be able to estimate the amount of Tinopal SWN, 25% of the measured data from the SysDEA experiments were used to calibrate by correlating the summed pixel values from the photographs to actual measured exposure values using a second order regression model. For spraying both high and low viscosity liquids, showing uniformly distributed exposure patterns, strong Pearson correlation coefficients (R > 0.77) were observed. In contrast, the correlations were either inconsistently poor (R = -0.17 to 0.28 for pouring, rolling high viscosity liquid, manually handling objects immersed in low viscosity liquid and handling objects contaminated with powder), moderate (R = 0.73 for dumping of powder), or strong (R = 0.83 and 0.77 for rolling low viscosity liquid and manually handling objects immersed in high viscosity liquid). A model for spraying was developed and calibrated using 25% of the available experimental data for spraying and validated using the remaining 75%. Under given experimental conditions, the fluorescence method shows promising results and can be used for the quantification of dermal exposure for different body parts (excluding hands) for spraying-like scenarios that have a more uniform exposure pattern, but more research is needed for exposure scenarios with less uniform exposure patterns. For the estimation of exposure levels, the surface loading limit should be lower than 1.5░µg/cm2 (a lower limit could not be quantified based on experiments conducted in this study) on a large surface, like a coverall, which should be ideally perpendicular to the camera.

Occupational Exposure to Diisocyanates in the European Union.

OBJECTIVES: Diisocyanates are a chemical group that are widely used at workplaces in many sectors. They are also potent skin- and respiratory sensitizers. Exposure to diisocyanates is a main cause of occupational asthma in the European Union. To reduce occupational exposure to diisocyanates and consequently the cases of diisocyanate-induced asthma, a restriction on diisocyanates was recently adopted under the REACH Regulation in the European Union. METHODS: A comprehensive evaluation of the data on occupational exposure to the most important diisocyanates at workplaces was made and is reported here. The diisocyanates considered are methylene diphenyl diisocyanate (MDI), toluene diisocyanate (TDI), and hexamethylene diisocyanate (HDI), accounting for more than 95% of the market volume in the EU. The exposure assessment is based on data from Chemical Safety Reports (CSRs) of REACH Registration Dossiers, workplace air monitoring data from Germany, from the UK Health and Safety Executive (HSE), and literature data relevant for the EU, and the USA. RESULTS: Occupational exposure to diisocyanates is particularly relevant in: (i) C.A.S.E. applications (Coatings, Adhesives, Sealants, Elastomers), (ii) production of polyurethanes (PUs) (e.g. slab-stock foam), (iii) handling of partly uncured PU products (e.g. cutting, demoulding, spray application of foam), and (iv) when diisocyanates/PUs are heated (e.g. hot lamination, foundry applications/casting forms). Ranking of the reported data on inhalation to diisocyanate exposure at workplaces (maximum values) leads to following order: (i) HDI and its oligomers in coatings, (ii) MDI in spray foam applications, (iii) TDI in manufacture of foam, (iv) TDI in manufacture of PUs and PU composite materials, (v) TDI in adhesives, (vi) MDI in adhesives, (vii) MDI in manufacture of PUs and PU composite materials, (viii) TDI in coatings, (ix) MDI in manufacture of foam, and (x) HDI in adhesives.

Building a European exposure science strategy.

Exposure information is a critical element in various regulatory and non-regulatory frameworks in Europe and elsewhere. Exposure science supports to ensure safe environments, reduce human health risks, and foster a sustainable future. However, increasing diversity in regulations and the lack of a professional identity as exposure scientists currently hamper developing the field and uptake into European policy. In response, we discuss trends, and identify three key needs for advancing and harmonizing exposure science and its application in Europe. We provide overarching building blocks and define six long-term activities to address the identified key needs, and to iteratively improve guidelines, tools, data, and education. More specifically, we propose creating European networks to maximize synergies with adjacent fields and identify funding opportunities, building common exposure assessment approaches across regulations, providing tiered education and training programmes, developing an aligned and integrated exposure assessment framework, offering best practices guidance, and launching an exposure information exchange platform. Dedicated working groups will further specify these activities in a consistent action plan. Together, these elements form the foundation for establishing goals and an action roadmap for successfully developing and implementing a 'European Exposure Science Strategy' 2020-2030, which is aligned with advances in science and technology.

Comparison of Measurement Methods for Dermal Exposure to Hazardous Chemicals at the Workplace: The SysDEA Project.

There is a principal need for more precise methodology with regard to the determination of occupational dermal exposure. The goal of the Systematic analysis of Dermal Exposure to hazardous chemical Agents at the workplace project was therefore to generate scientific knowledge to improve and standardize measurement methods for dermal exposure to chemicals at the workplace. In addition, the comparability of different measurement methods was investigated. Different methods (body sampling by means of coveralls and patches, hand sampling by means of gloves and washing, and head sampling by means of headbands and wiping) were compared. Volunteers repeatedly performed a selection of tasks under standardized conditions in test chambers to increase the reproducibility and decrease variability. The selected tasks were pouring, rolling, spraying, and handling of objects immersed in liquid formulations, as well as dumping and handling objects contaminated with powder. For the chemical analysis, the surrogate test substance Tinopal SWN was analyzed by means of a high-performance liquid chromatographic method using a fluorescence detector. Tinopal SWN was either applied as a solid product in its pure form, or as a low and high viscosity liquid containing Tinopal SWN in dissolved form. To compare the sampling methods with patches and coveralls, the exposure values as measured on the patches were extrapolated to the surface areas of the respective parts of the coverall. Based on this extrapolation approach, using the patch method resulted in somewhat higher exposure values compared to using a coverall for all exposure situations, but the differences were only statistically significant in case of the liquid exposure situations. Using gloves resulted in significantly higher exposure values compared to hand wash for handling immersed objects, rolling, and handling contaminated objects, and slightly higher (not significant) exposure values during pouring and spraying. In the same context, applying wipe sampling resulted in higher exposure values than using a headband, which was at least partly due to extrapolation of the wipe results to the surface area of the headband. No 'golden standard' with regard to a preferred measurement method for dermal exposure could be identified from the methods as investigated in the current study.

Synthesis of N-unsubstituted, mono- and disubstituted carbohydrate-1-O-carbamates and their behaviour in glycoside syntheses.

The syntheses of 44 1-carbamates from six different 1-O-unprotected carbohydrate derivatives (compounds 1-6), representing typical protecting pattern in glycoside synthesis, are described. The carbamate function is N-unsubstituted (compounds 1b-6b), mono- (compounds a: N-trichloroacetyl, c: N-monochloroacetyl, d: N-acetyl, e: N-ethyl, f: N-allyl, g: N-phenyl) or disubstituted (compounds h: imidazolyl, i: N-diethyl, j: N-diphenyl). Additionally, three N-chlorosulfonyl carbamates are synthesized and used as intermediates for the synthesis of N-unsubstituted compounds b. The accessibility of these compounds is described and compared. Some of the carbamates (1, 4, 5a-j) are used as model compounds for systematic investigations in glycoside syntheses. Selected experimental data (reaction conditions, anomeric ratios, rotation values, selected NMR data) are tabulated.