HD Physiology Project-Japanese efforts to promote multilevel integrative systems biology and physiome research.

The HD Physiology Project is a Japanese research consortium that aimed to develop methods and a computational platform in which physiological and pathological information can be described in high-level definitions across multiple scales of time and size. During the 5 years of this project, an appropriate software platform for multilevel functional simulation was developed and a whole-heart model including pharmacokinetics for the assessment of the proarrhythmic risk of drugs was developed. In this article, we outline the description and scientific strategy of this project and present the achievements and influence on multilevel integrative systems biology and physiome research

Sustainability of the chemical manufacturing industry - Towards a new paradigm?

This paper describes the current situation of the chemicalmanufacturingindustry, with special reference to Europe and looks to the future sustainability demands on the sector, and the implications of these demands for chemical engineering education. These implications include definitions of sustainability criteria for the sector and the need for transparent reporting under the Triple Bottom Line approach. The response of the education system to the sustainability agenda over the years and a number of strategies to incorporate it into courses are described. The important role of chemical (or more generally, process) engineers in delivering sustainable solutions is emphasised but this also suggests that anew way of thinking about the discipline is required. Indeed, this paper argues that the demand for a sustainable chemicalmanufacturing sector could bring about the next paradigm shift in the discipline which has been predicted for some time

Review of Life Cycle Assessment in Agro-Chemical Processes

Life Cycle Assessment (LCA) is a method used to evaluate the potential impacts on the environment of a product, process, or activity throughout its life cycle. Today’s LCA users are a mixture of individuals with skills in different disciplines who want to evaluate their products, processes, or activities in a life cycle context. This study attempts to present some of the LCA studies on agro-chemical processes, recent advances in LCA and their application on food products and non-food products. Due to the recent development of LCA methodologies and dissemination programs by international and local bodies, use of LCA is rapidly increasing in agricultural and industrial products. The literatures suggest that LCA coupled with other environmental approaches provides much more reliable and comprehensive information to environmentally conscious policy makers, producers, and consumers in selecting sustainable products and production processes. For this purpose, a field study of LCA of biodiesel from Jatropha curcas has been taken as an example in the study. In the past, LCA has been applied primarily to products but recent literature suggests that it has also the potential as an analysis and design tool for processes and services. In general, all primary industries use energy and water resources and emit pollutants gases. LCA is a method to report on and analyze these resource issues across the life cycle of agro-chemical processes. This review has the importance as a first part of a research project to develop a life cycle assessment methodology for agro-chemical industries. It presents the findings of a literature review that focuses on LCA of agriculture and chemical engineering literatur

Policy Makers’ Influence on the Emergence of a New Scientific Discipline: The Case of Nanotechnology in Ireland

Science has undergone tremendous changes since World War II with the blurring of boundaries between science, government, and industry, as well as the so-called convergence of scientific disciplines. Nanotechnology is an illustrative example of this phenomenon. Boundaries between all these spheres are challenged, renegotiated, and reshaped under the influence of the multiple actors involved. I question here the extent to which nanoscience and nanotechnology (N&N) are emerging as a new scientific discipline under the influence of science and technology policies. With the study of N&N in Ireland from the late 1990s onwards, a focus is placed on both the macro-meso and meso-micro levels of analysis. Through a comparative case study research design of six research teams, I describe that policy makers have, to a certain extent, restructured the physical boundaries of science to make them conform to the nanotechnology logic, whereas the social and mental boundaries are still ruled by an established paradigm logic. This is confirmed at the meso-micro level with the identification of the barriers that scientists with diverse backgrounds face in a multidisciplinary laboratory. Thus, nanotechnology as a general purpose technology has challenged and renewed our theoretical conceptions of technology management by affording possibilities for both radical and incremental innovations. Moreover, even though policy makers are more involved in the scientific activity, they have a limited impact on it by not being able to steer the cognitive structure of science. Boundaries, in these types of organisations, instead of being blurred, are becoming ever more complex

partnering to strengthen Risk‐Benefit Assessment within the EU using a holistic approach

publishersversionpublishe

Scientific methodologies for the assessment of combined effects of chemicals - a survey and literature review

Exposure of humans and wildlife to chemicals via food, consumer products, the environment etc. can imply exposure to an infinite number of different combinations of chemicals in mixtures. It is practically impossible to test all these possible mixtures experimentally and it is therefore needed to find smart strategies to assess the potential hazards using new tools that rely less on in vivo testing and incorporate instead alternative experimental and computational tools. In this report the current state of the art for the application of these alternative tools for assessing the hazard of chemical mixtures is briefly reviewed. The focus is hereby on the adverse outcome pathway (AOP) concept, in vitro methods, omics techniques, in silico approaches such as quantitative structure activity relationships (QSARs) and read-across, toxicokinetic and dynamic energy budget (DEB) modelling, and on integrated approaches to testing and assessment (IATA). Furthermore, an expert survey was performed to collect up to date information and experience on the current use of different approaches for assessing human and environmental health risks from exposure to chemical mixtures, with a view to informing the development of a consistent assessment approach. An online survey was performed among experts in the field of combined exposure assessment in the period of January to March 2014, addressing both, human health and environmental risk assessment. Fifty-eight experts from 21 countries, different stakeholder groups and sectors of legislation participated in the survey. The main sectors where most experience is already gained in assessing mixtures are in the area of plant protection products and chemicals. These were also rated highest regarding the priority for performing mixture assessments. Experts have experience with the whole mixture as well as the component-based approaches applying them to both, intentional and unintentional mixtures. Mostly concentration addition (CA) based methods are used for predicting mixture effects. Regarding the use of novel and alternative tools in the risk assessment of mixtures, expert opinions are split between those applying them (often more in a research context) and those that generally think these tools are valuable but their use is currently limited because of lack of guidance, lack of data, or lack of expertise. A general need for clear guidance for combined exposure assessments was identified. Overall, a high potential in applying novel tools and scientific methodologies for the assessment of chemical mixtures can be identified. They allow deriving meaningful information on individual mixture components or whole mixtures, enabling a better understanding of the underlying mechanisms of mixture effects. Their main strengths lie in their integrated use and smart combination to put different aspects regarding the hazard from combined exposure to multiple chemicals into context. In order to benefit from these tools in the hazard assessment of mixtures, more guidance on their use is needed to facilitate a more widespread application.JRC.I.5-Systems Toxicolog

Application of AOPs to assist regulatory assessment of chemical risks – Case studies, needs and recommendations

While human regulatory risk assessment (RA) still largely relies on animal studies, new approach methodologies (NAMs) based on in vitro, in silico or non-mammalian alternative models are increasingly used to evaluate chemical hazards. Moreover, human epidemiological studies with biomarkers of effect (BoE) also play an invaluable role in identifying health effects associated with chemical exposures. To move towards the next generation risk assessment (NGRA), it is therefore crucial to establish bridges between NAMs and standard approaches, and to establish processes for increasing mechanistically-based biological plausibility in human studies. The Adverse Outcome Pathway (AOP) framework constitutes an important tool to address these needs but, despite a significant increase in knowledge and awareness, the use of AOPs in chemical RA remains limited. The objective of this paper is to address issues related to using AOPs in a regulatory context from various perspectives as it was discussed in a workshop organized within the European Union partnerships HBM4EU and PARC in spring 2022. The paper presents examples where the AOP framework has been proven useful for the human RA process, particularly in hazard prioritization and characterization, in integrated approaches to testing and assessment (IATA), and in the identification and validation of BoE in epidemiological studies. Nevertheless, several limitations were identified that hinder the optimal usability and acceptance of AOPs by the regulatory community including the lack of quantitative information on response-response relationships and of efficient ways to map chemical data (exposure and toxicity) onto AOPs. The paper summarizes suggestions, ongoing initiatives and third-party tools that may help to overcome these obstacles and thus assure better implementation of AOPs in the NGRA.European Commission 733032 857560 101057014Ministry of Education, Youth and Sports by the RECETOX Research Infrastructure LM2018121OP RDE project CETOCOEN Excellence CZ.02.1.01/0.0/0.0/17_043/0009632Japan Agency for Medical Research and Development (AMED) JP21mk0101216 JP22mk0101216Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of ScienceGrants-in-Aid for Scientific Research (KAKENHI) 21K1213

Application of AOPs to assist regulatory assessment of chemical risks - Case studies, needs and recommendations

While human regulatory risk assessment (RA) still largely relies on animal studies, new approach methodologies (NAMs) based on in vitro, in silico or non-mammalian alternative models are increasingly used to evaluate chemical hazards. Moreover, human epidemiological studies with biomarkers of effect (BoE) also play an invaluable role in identifying health effects associated with chemical exposures. To move towards the next generation risk assessment (NGRA), it is therefore crucial to establish bridges between NAMs and standard approaches, and to establish processes for increasing mechanistically-based biological plausibility in human studies. The Adverse Outcome Pathway (AOP) framework constitutes an important tool to address these needs but, despite a significant increase in knowledge and awareness, the use of AOPs in chemical RA remains limited. The objective of this paper is to address issues related to using AOPs in a regulatory context from various perspectives as it was discussed in a workshop organized within the European Union partnerships HBM4EU and PARC in spring 2022. The paper presents examples where the AOP framework has been proven useful for the human RA process, particularly in hazard prioritization and characterization, in integrated approaches to testing and assessment (IATA), and in the identification and validation of BoE in epidemiological studies. Nevertheless, several limitations were identified that hinder the optimal usability and acceptance of AOPs by the regulatory community including the lack of quantitative information on response-response relationships and of efficient ways to map chemical data (exposure and toxicity) onto AOPs. The paper summarizes suggestions, ongoing initiatives and third-party tools that may help to overcome these obstacles and thus assure better implementation of AOPs in the NGRA