Potential harmful health effects of inhaling nicotine-free shisha-pen vapor: a chemical risk assessment of the main components propylene glycol and glycerol

Background A shisha-pen is an electronic cigarette variant that is advertised to mimic the taste of a water pipe, or shisha. The aim of this study was to assess the potential harmful health effects caused by inhaling the vapor of a nicotine-free shisha-pen. Methods Gas chromatography analysis was performed to determine the major components in shisha-pen vapor. Risk assessment was performed using puff volumes of e-cigarettes and “normal” cigarettes and a 1-puff scenario (one-time exposure). The concentrations that reached the airways and lungs after using a shisha-pen were calculated and compared to data from published toxicity studies. Results The main components in shisha-pen vapor are propylene glycol and glycerol (54%/46%). One puff (50 to 70 mL) results in exposure of propylene glycol and glycerol of 430 to 603 mg/m3 and 348 to 495 mg/m3, respectively. These exposure concentrations were higher than the points of departure for airway irritation based on a human study (propylene glycol, mean concentration of 309 mg/m3) and a rat study (glycerol, no-observed adverse effect level of 165 mg/m3). Conclusions Already after one puff of the shisha-pen, the concentrations of propylene glycol and glycerol are sufficiently high to potentially cause irritation of the airways. New products such as the shisha-pen should be detected and risks should be assessed to inform regulatory actions aimed at limiting potential harm that may be caused to consumers and protecting young people to take up smoking

In vitro data combined with human disease data to improve toxicological hazard assessment: the ASAT Knowledge Base

In line with the Assuring Safety Without Animal Testing (ASAT) principle, risk assessment may ultimately become feasible without the use of animals (Fentem et al., 2004). ASAT assumes that activation of human disease mechanisms in in vitro models can be used for toxicological assessment. Therefore, goal of the present research was to demonstrate the integration of public data from the human disease domain with in vitro toxicology. Two diseases, associated with chemical exposure, were concerned: hepatocellular carcinoma and allergic contact dermatitis (ACD). Data were retrieved from online sources (e.g., GEO, CTD) and expert knowledge. A Knowledge Base for curation, storage and modelling of the data was developed. Using the Knowledge Base for ACD, it was possible to discern sensitizing from non-sensitizing chemicals, as defined by enrichment of disease gene sets in in vitro toxicogenomics datasets. Interestingly, the strongest sensitizers most profoundly activated these gene sets. The ongoing incorporation of (reverse) PBPK models in the Knowledge Base to judge the relevance of in vitro concentrations, in relation to realistic in vivo exposure scenarios, will be presented. Finally, the expansion with models towards other disease areas (cholestasis) will be discussed

A roadmap to strengthen standardisation efforts in risk governance of nanotechnology.

International audienceA roadmap was developed to strengthen standardisation activities for risk governance of nanotechnology. Its baseline is the available standardised and harmonised methods for nanotechnology developed by the International Organization for Standardization (ISO), the European Committee for Standardization (CEN), and the Organisation for Economic Co-operation and Development (OECD). In order to identify improvements and needs for new themes in standardisation work, an analysis of the state-of-the-art concepts and interpretations of risk governance of nanotechnology was performed. Eleven overall areas of action were identified, each including a subset of specific topics. Themes addressed include physical chemical characterisation, assessment of hazard, exposure, risk and socio-economic factors, as well as education & training and social dialogue. This has been visualised in a standardisation roadmap spanning a timeframe of ten years and including key outcomes and highlights of the analysis. Furthermore, the roadmap indicates potential areas of action for harmonisation and standardisation (H&S) for nanomaterials and nanotechnology. It also includes an evaluation of the current level (limited, moderate, intense) of ongoing H&S activities and indicates the time horizon for the different areas of action. As the identified areas differ in their state of development, the number and type of actions varied widely amongst the different actions towards achieving standardisation. Thus, priority areas were also identified. The overall objective of these actions is to strengthen risk governance towards a safe use of nanomaterials and nano-related products. Though not explicitly addressed, risk-based legislation and policies are supported via the proposed H&S actions

Assuring safety without animal testing concept (ASAT). Integration of human disease data with in vitro data to improve toxicology testing

According to the Assuring Safety Without Animal Testing (ASAT) principle, risk assessment may ultimately become possible without the use of animals (Fentem et al., (2004). Altern. Lab. Anim. 32, 617-623). The ASAT concept takes human disease mechanisms as starting point and tries to define if activation of these mechanisms by chemical exposure in in vitro models can be used for toxicological risk assessment. The goal of the present research was to study if integration of public data, from human diseases and in vitro toxicology, is possible at the data level. Two human diseases, associated with chemical exposure, were included: human hepatocellular carcinoma and allergic contact dermatitis (ACD). Data were retrieved from expert knowledge and different online sources (e.g. GEO, ArrayExpress) and a Knowledge Base for storage and modelling of the data was established. Using the Knowledge Base for ACD, it was possible to discern sensitizing from non-sensitizing compounds, as defined by enrichment of clinically defined disease gene sets in in vitro genomics datasets. In addition, the strongest sensitizers most profoundly activated these gene sets. During the presentation, the Knowledge Base will be shown. In addition, the ongoing incorporation of (reverse) kinetic modelling to judge the relevance of in vitro concentrations, in relation to realistic in vivo exposure scenarios, will be illustrated. Finally, the expansion towards the development of data models for other disease areas (cholestasis) will be discussed

Governance of advanced materials:Shaping a safe and sustainable future

The past few decades of managing the uncertain risks associated with nanomaterials have provided valuable insights (knowledge gaps, tools, methods, etc.) that are equally important to promote safe and sustainable development and use of advanced materials. Based on these insights, the current paper proposes several actions to optimize the risk and sustainability governance of advanced materials. We emphasise the importance of establishing a European approach for risk and sustainability governance of advanced materials as soon as possible to keep up with the pace of innovation and to manage uncertainty among regulators, industry, SMEs and the public, regarding potential risks and impacts of advanced materials. Coordination of safe and sustainable advanced material research efforts, and data management according to the Findable, Accessible, Interoperable and Reusable (FAIR) principles will enhance the generation of regulatory-relevant knowledge. This knowledge is crucial to identify whether current regulatory standardised and harmonised test methods are adequate to assess advanced materials. At the same time, there is urgent need for responsible innovation beyond regulatory compliance which can be promoted through the Safe and Sustainable Innovation Approach. that combines the Safe and Sustainable by Design concept with Regulatory Preparedness, supported by a trusted environment. We further recommend consolidating all efforts and networks related to the risk and sustainability governance of advanced materials in a single, easy-to-use digital portal. Given the anticipated complexity and tremendous efforts required, we identified the need of establishing an organisational structure dedicated to aligning the fast technological developments in advanced materials with proper risk and sustainability governance. Involvement of multiple stakeholders in a trusted environment ensures a coordinated effort towards the safe and sustainable development, production, and use of advanced materials. The existing infrastructures and network of experts involved in the governance of nanomaterials would form a solid foundation for such an organisational structure.</p