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.

Silicon, silica and its surface patterning/activation with alkoxy- and amino-silanes for nanomedical applications.

Silica and silicates are widely used in nanomedicine with applications as diverse as medical device coatings to replacement materials in tissue engineering. Although much is known about silica and its synthesis, relatively few biomedical scientists fully appreciate the link that exists between its formulation and its resultant structure and function. This article attempts to provide insight into relevant issues in that context, as well as highlighting their importance in the material's eventual surface patterning/activation with alkoxy- and organo-silanes. The use of aminosilanes in that context is discussed at some length to permit an understanding of the specific variables that are important in the reproducible and robust aminoactivation of surfaces using such molecules. Recent investigative work is cited to underline the fact that although aminosilanization is a historically accepted mechanism for surface activation, there is still much to be explained about how and why the process works in the way it does. In the last section of this article, there is a detailed discussion of two classical approaches for the use of aminosilanized materials in the covalent immobilization of bioligands, amino-aldehyde and amino-carboxyl coupling. In the former case, the use of the homobifunctional coupler glutaraldehyde is explored, and in the latter, carbodiimides. Although these chemistries have long been employed in bioconjugations, it is apparent that there are still variables to be explored in the processes (as witnessed by continuing investigations into the chemistries concerned). Aspects regarding optimization, standardization and reproducibility of the fabrication of amino functionalized surfaces are discussed in detail and illustrated with practical examples to aid the reader in their own studies, in terms of considerations to be taken into account when producing such materials. Finally, the article attempts to remind readers that although the chemistry and materials involved are 'old hat', there is still much to be learnt about the methods involved. The article also reminds readers that although many highly specific and costly conjugation chemistries now exist for bioligands, there still remains a place for these relatively simple and cost-effective approaches in bioligand conjugate fabrication.

Dipodal ferrocene-based adsorbate molecules for self-assembled monolayers on gold.

1,1'-Difunctionalised ferrocene derivatives have been studied, which contain groups suitable for chemisorption on gold substrates, namely -NC, -PR(2) as well as a range of sulfur-containing units like -NCS, -SR, and thienyl. Thin films on gold have been fabricated from solution with most of these adsorbate species. Film thickness, composition and structure were investigated primarily by X-ray photoelectron and near-edge X-ray absorption fine-structure spectroscopy. The quality of self-assembled monolayers fabricated from 1,1'-diisocyanoferrocene (1) and 1,1'-diisothiocyanatoferrocene (2) turned out to be superior to that of films based on the other adsorbate species investigated. In addition to the surface coordination behaviour of 1 towards gold substrates, relevant aspects of the molecular coordination chemistry of 1 have also been addressed, including the synthesis and characterisation of [(mu-1){Cr(CO)(5)}(2)], [Ag(2)(mu-1)(2)](NO(3))(2) x H(2)O and [(mu-1)(AuCl)(2)]. The crystal structure of the gold complex is governed by aurophilic interactions and can be taken as a model for the arrangement of 1 in self-assembled monolayers on gold.

"Schizoid" reactivity of 1,1'-diisocyanoferrocene.

The two chemically equivalent functional groups of 1,1'-diisocyanoferrocene each undergo a different specific reaction with the gold(I) acetylide [Au(C=C-Fc)], viz. ordinary coordination and extraordinary 1,1-insertion.

The interaction of 1,1'-diisocyanoferrocene with gold: formation of monolayers and supramolecular polymerization of an aurophilic ferrocenophane.

The coordination chemistry of 1,1'-diisocyanoferrocene (1) was investigated. Its reaction with Cr(CO)5(THF) (2 equiv) affords (1)[Cr(CO)5]2, which exhibits eclipsed cyclopentadienyl rings with a synclinal arrangement of the two substituents. 1 behaves like an aryl isocyanide in this compound according to IR spectroscopic data, and its oxidation leads to a marked decrease of net electron donor ability. The reaction of 1 with AuCl(SMe2) affords the insoluble coordination polymer [(1)(AuCl)2]infinity. The (1)(AuCl)2 molecules adopt a 3,4-diaura-[6]ferrocenophane structure. They are aggregated in a zipperlike fashion through aurophilic interactions, with Au-Au distances ranging from 3.34 to 3.48 A. The adsorption of 1 from acetonitrile solution on polycrystalline gold affords a self-assembled monolayer. Both isocyanide groups are binding to the surface.