Nano or Not Nano? A Structured Approach for Identifying Nanomaterials According to the European Commission's Definition.

Identifying nanomaterials (NMs) according to European Union legislation is challenging, as there is an enormous variety of materials, with different physico-chemical properties. The NanoDefiner Framework and its Decision Support Flow Scheme (DSFS) allow choosing the optimal method to measure the particle size distribution by matching the material properties and the performance of the particular measurement techniques. The DSFS leads to a reliable and economic decision whether a material is an NM or not based on scientific criteria and respecting regulatory requirements. The DSFS starts beyond regulatory requirements by identifying non-NMs by a proxy approach based on their volume-specific surface area. In a second step, it identifies NMs. The DSFS is tested on real-world materials and is implemented in an e-tool. The DSFS is compared with a decision flowchart of the European Commission's (EC) Joint Research Centre (JRC), which rigorously follows the explicit criteria of the EC NM definition with the focus on identifying NMs, and non-NMs are identified by exclusion. The two approaches build on the same scientific basis and measurement methods, but start from opposite ends: the JRC Flowchart starts by identifying NMs, whereas the NanoDefiner Framework first identifies non-NMs.

NanoDefiner Framework and e-Tool Revisited According to the European Commission's Nanomaterial Definition 2022/C 229/01.

The new recommended definition of a nanomaterial, 2022/C 229/01, adopted by the European Commission in 2022, will have a considerable impact on European Union legislation addressing chemicals, and therefore tools to implement this new definition are urgently needed. The updated NanoDefiner framework and its e-tool implementation presented here are such instruments, which help stakeholders to find out in a straightforward way whether a material is a nanomaterial or not. They are two major outcomes of the NanoDefine project, which is explicitly referred to in the new definition. This work revisits the framework and e-tool, and elaborates necessary adjustments to make these outcomes applicable for the updated recommendation. A broad set of case studies on representative materials confirms the validity of these adjustments. To further foster the sustainability and applicability of the framework and e-tool, measures for the FAIRification of expert knowledge within the e-tool's knowledge base are elaborated as well. The updated framework and e-tool are now ready to be used in line with the updated recommendation. The presented approach may serve as an example for reviewing existing guidance and tools developed for the previous definition 2011/696/EU, particularly those adopting NanoDefine project outcomes.

Prevalence of STIs, sexual practices and substance use among 2083 sexually active unmarried women in Lebanon.

Access to sexual and reproductive health in conservative communities and in the MENA region are particularly limited and, as such, increase women's vulnerability to unwanted pregnancies, unsafe abortions, and sexually transmitted infections (STIs). The aim was to assess the prevalence of STIs, sexual practices, recreational drug-use and their possible associations among cisgender unmarried women residing in Lebanon. Data on demographics, sexual practices and substance-use were collected from 2083 unmarried cisgender women who voluntarily attended a sexual health clinic in Lebanon between 2015 and 2019. They tested for HIV, Hepatitis B, Hepatitis C and Syphilis through rapid testing. Other infections (genital warts, Neisseria gonorrhea/Chlamydia trachomatis) were screened for. Regression models were computed between variables. There were two cases of HIV, one of Hepatitis B and syphilis, and no cases of Hepatitis C. Genital warts were present in 15% and symptoms indicative of Neisseria gonorrhea/Chlamydia trachomatis in 14%. Inconsistent condom-use (81%) was significantly associated with number of partners (adj. OR: 0.4). Inconsistent condom-use discussion with partners (33%) was significantly associated with unemployment (adj OR: 1.7), recreational drug-use (adj. OR: 1.4), and number of partners (adj. ORs 3.7-4.4). Unwanted pregnancies (11%) were significantly associated with age (adj. ORs 0.1-0.37), recreational drug-use (adj. OR: 2), using intrauterine device (adj. OR:2.9) and natural birth control methods (adj. OR: 2.4). Recreational drug-use (33%) was significantly associated with age (adj ORs 1.9-2.2), and smoking status (adj. OR: 0.6). The results indicate an urgent need for: (1) Accessible, non-stigmatizing, and inclusive sexual health services dedicated to women's sexual health; (2) Comprehensive and non-stigmatizing sexual health education for all, but especially women, in order to promote safer sexual practices and effective decision making with regards to contraception and condom-use.

A technique-driven materials categorisation scheme to support regulatory identification of nanomaterials.

Worldwide there is a variety of regulatory provisions addressing nanomaterials. The identification as nanomaterial in a regulatory context often has the consequence that specific legal rules apply. In identifying nanomaterials, and to find out whether nanomaterial-specific provisions apply, the external size of particles is globally used as a criterion. For legal certainty, its assessment for regulatory purposes should be based on measurements and methods that are robust, fit for the purpose and ready to be accepted by different stakeholders and authorities. This should help to assure the safety of nanomaterials and at the same time facilitate their international trading. Therefore, we propose a categorisation scheme which is driven by the capabilities of common characterisation techniques for particle size measurement. Categorising materials according to this scheme takes into account the particle properties that are most important for a determination of their size. The categorisation is exemplified for the specific particle number based size metric of the European Commission's recommendation on the definition of nanomaterial, but it is applicable to other metrics as well. Matching the performance profiles of the measurement techniques with the material property profiles (i) allows selecting the most appropriate size determination technique for every type of material considered, (ii) enables proper identification of nanomaterials, and (iii) has the potential to be accepted by regulators, industry and consumers alike. Having such a scheme in place would facilitate the regulatory assessment of nanomaterials in regional legislation as well as in international relations between different regulatory regions assuring the safe trade of nanomaterials.

Prevalence of HIV and other sexually transmitted infections and their association with sexual practices and substance use among 2238 MSM in Lebanon.

UNAIDS report documents 95% increase in new HIV infections among key populations in Eastern Europe and Middle East and North Africa region. Data on HIV and STIs among MSM in Lebanon is still scarce. Therefore, the aim was to assess prevalence of HIV and sexually transmitted infections (STIs) among men who have sex with men (MSM) in Lebanon and associations with sexual practices and substance-use. 2238 MSM attended a sexual health clinic in Lebanon between 2015-2018. Demographics, substance-use and sexual practices were collected. Attendees tested for HIV and other STIs. HIV infection was diagnosed in 5.6% of the sample. Only 19% received sexual health education from reliable sources (school/university/healthcare workers), 78% reported having multiple partners in the past three months (2-5 partners: 58%, 6+: 20%) and 67% reported inconsistent condom-use. Moreover, 40% of HIV + cases were returning attendees who already received information about condom-use. Additionally, having only a school level education (11%) increases the odds of having inconsistent condom-use with casual partners (adj.OR:1.9, p < 0.001). The results reflect the urgent need for: (1) accurate and comprehensive sexual health and harm reduction education and promotion in Lebanon; (2) making pre-exposure prophylaxis available for free to key populations to contain the epidemics at an early stage.

NanoDefiner e-Tool: An Implemented Decision Support Framework for Nanomaterial Identification.

The European Commission's recommendation on the definition of nanomaterial (2011/696/EU) established an applicable standard for material categorization. However, manufacturers face regulatory challenges during registration of their products. Reliable categorization is difficult and requires considerable expertise in existing measurement techniques (MTs). Additionally, organizational complexity is increased as different authorities' registration processes require distinct reporting. The NanoDefine project tackled these obstacles by providing the NanoDefiner e-tool: A decision support expert system for nanomaterial identification in a regulatory context. It provides MT recommendations for categorization of specific materials using a tiered approach (screening/confirmatory), and was constructed with experts from academia and industry to be extensible, interoperable, and adaptable for forthcoming revisions of the nanomaterial definition. An implemented MT-driven material categorization scheme allows detailed description. Its guided workflow is suitable for a variety of user groups. Direct feedback and explanation enable transparent decisions. Expert knowledge is held in a knowledge base for representation of MT performance criteria and physicochemical particle type properties. Continuous revision ensured data quality and validity. Recommendations were validated by independent case studies on industry-relevant particulate materials. Besides supporting material identification and registration, the free and open-source e-tool may serve as template for other expert systems within the nanoscience domain.

Reliable nanomaterial classification of powders using the volume-specific surface area method.

The volume-specific surface area (VSSA) of a particulate material is one of two apparently very different metrics recommended by the European Commission for a definition of "nanomaterial" for regulatory purposes: specifically, the VSSA metric may classify nanomaterials and non-nanomaterials differently than the median size in number metrics, depending on the chemical composition, size, polydispersity, shape, porosity, and aggregation of the particles in the powder. Here we evaluate the extent of agreement between classification by electron microscopy (EM) and classification by VSSA on a large set of diverse particulate substances that represent all the anticipated challenges except mixtures of different substances. EM and VSSA are determined in multiple labs to assess also the level of reproducibility. Based on the results obtained on highly characterized benchmark materials from the NanoDefine EU FP7 project, we derive a tiered screening strategy for the purpose of implementing the definition of nanomaterials. We finally apply the screening strategy to further industrial materials, which were classified correctly and left only borderline cases for EM. On platelet-shaped nanomaterials, VSSA is essential to prevent false-negative classification by EM. On porous materials, approaches involving extended adsorption isotherms prevent false positive classification by VSSA. We find no false negatives by VSSA, neither in Tier 1 nor in Tier 2, despite real-world industrial polydispersity and diverse composition, shape, and coatings. The VSSA screening strategy is recommended for inclusion in a technical guidance for the implementation of the definition. Graphical abstractWe evaluate the extent of agreement between classification by electron microscopy (EM) and classification by Volume-Specific Surface Area (VSSA) on a large set of diverse particulate substances. These represent the challenges anticipated for identification of nanomaterials by the European Commission recommendation for a definition of nanomaterials for regulatory purposes.

Nanocrystals: comparison of the size reduction effectiveness of a novel combinative method with conventional top-down approaches.

Nanosizing is a non-specific approach to improve the oral bioavailability of poorly soluble drugs. The decreased particle size of these compounds results in an increase in surface area. The outcome is an increased rate of dissolution, which can lead to a better oral absorption. Standard approaches are bottom-up and top-down techniques. Combinative technologies are relatively new approaches, and they can be described as a combination of a bottom-up process followed by a top-down step. The work presented in this paper can be described as a combination of a non-aqueous freeze drying step (bottom-up), followed by wet ball milling or high pressure homogenization (top-down) to produce fine drug nanocrystals. The crystal habit of the model drug glibenclamide was modified by freeze drying from dimethyl sulfoxide (DMSO)/tert-butanol (TBA) solvent mixtures using different ratios. The resulting drug powders were characterized by scanning electron microscopy (SEM) as well as by X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). It was shown that the combinative approach can significantly improve the particle size reduction effectiveness of both top-down methods over conventional approaches. Drug lyophilization using DMSO:TBA in 25:75 and 10:90 v/v ratios resulted in a highly porous and breakable material. The milling time to achieve nanosuspensions was reduced from 24h with the jet-milled glibenclamide to only 1h with the modified starting material. The number of homogenization cycles was decreased from 20 with unmodified API to only 5 with the modified drug. The smallest particle size, achieved on modified samples, was 160nm by wet ball milling after 24h and 355nm by high pressure homogenization after 20 homogenization cycles at 1500bar.