Proposal template for a “ESA Topical Team” Title of the proposed Topical Team Topical Team on the Toxicity of Celestial Dusts (T3CD) Coordinator : Francesco Turci; University of Torino (ESA bidder code: 1000001029), Department of Chemistry, Via P. Giuria, 7 I-10125 – Torino, Italy; francesco.turci@unito.it; Office: +39 011 670 7566, Mobile: +39 348 573 4293 Members: Erin Tranfield (co-coordinator);Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, 2780-156 Oeiras, Portugal; etranfield@igc.gulbenkian.pt; +351 21 446 4691 Dag Linnarsson (past coordinator); Karolinska Institutet, Dept of Physiology and Pharmacology, Biomedicum Q6, Solnavägen 9, 171 77 Stockholm; Dag.Linnarsson@ki.se; +46 70 594 4401 Urs Staufer; Delft University of Technology, Dept. of Precision and Microsystems Engineering, Faculty of 3mE, Mekelweg 2, 2628 CD, Delft, The Netherlands; u.staufer@tudelft.nl; Tel: +31 15 2786804 Per Gerde; Karolinska Institutet; Institute of Environmental Medicine (IMM), Experimental asthma and allergy research, Imm/Eaaf Solnavägen 9, Kvarter 5b 171 65 Solna , Sweden; Per.Gerde@ki.se David J. Loftus; NASA Ames Research Center, Moffett Field, CA 94035, United States; david.j.loftus@nasa.gov Kim Prisk University of California, San Diego, Department of Medicine 9500 Gilman Drive La Jolla, CA 92093-0852, USA; +1-858-534-3233; kprisk@ucsd.edu Bice Fubini University of Torino, Department of Chemistry, via P. Giuria 7, I-10125 Torino, Italy; bice.fubini@unito.it; +39 011 670 7566 Lena Palmberg; Karolinska Institutet; Institute of Environmental Medicine (IMM), C6 Nobelsväg 13, 17177 Stockholm, Sweden; Lena.Palmberg@ki.se; +46 (0) 8-524 822 10 Lars Karlsson; Karolinska Institutet, Dept of Physiology and Pharmacology, Solna Vägen 9, B5 171 77, Solna, Sweden; Lars.Karlsson@ki.se; +46 (0) 8-524 868 90 1 Wim van Westrenen Department of Earth Sciences; Faculty of Science, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, Netherlands; w.van.westrenen@vu.nl Topical Team Coordinator signature: __________________ Date: January 18th, 2019 2 1. Proposal Abstract The Topical Team on the Toxicity of Celestial Dusts (T3CD) is composed by 11 well-respected scientists in a broad spectrum of disciplines, holding a wide range of complementary skills and expertise to address the most challenging questions in dust effects on human health. The team works in close contact with the ESA Human Space Exploration. T3CD aims to: O.1: identify the major knowledge gaps about celestial dust toxicity; O.2: propose standardized methodologies to estimate the inhalation health risk on celestial soil/dust; O.3: participate to research projects The objectives will be achieved through the following actions: A.1: Survey of activities on celestial dusts A.2: Propose standards methods for the handling, activation, passivation/inactivation kinetics, and curation of celestial dust analogues. A.3: Submit CORA proposal A.4: Propose experiments for celestial dust A.5: Participate to calls A.6: Attend workshops and conferences A.7: Prepare Roadmap Within the next two-year funding cycle, T3CD will deliver: D.1: Report to ESA with a review of the literature D.2: Internal report about standards required to develop a science-based knowledge of the toxicity of celestial dusts D.3: Project proposal under CORA to ESA D.4: Report experimental ideas and concepts to ESA D.5: Project proposal(s) shared with ESA D.6: Presentation of T3CD recommendations and contribution to workshop(s) D.7: Roadmap integration to ESA 2. Description of the topic to be addressed With a composition of international scientists holding a broad range of complementary skills and expertises in dust effects on human health, the Topical Team on the Toxicity of Celestial Dust (T3CD) provides ESA with scientific and technical advances in addressing the gaps in the scientific knowledge about features of the celestial dust and its toxicity. By filling such gaps, we provide scientifically based possibilities for mitigating the exposure of astronauts to potentially noxious dusts during planetary explorations and allow ESA to establish safe exposure limits. Habitats and vehicles shall be designed so that exposures of crews to celestial dusts would be limited to safe levels 3 3. Description of proposed work The TT will achieve the defined goals and objectives by implementing a multidirectional strategy with the following actions: Meetings, Participation to Local and European Calls, Interaction with SMEs, Preliminary Experimental Work, Participation to Ground based facility (CORA) programme call. Detailed description of the work is reported in Annex 2 (par. 1.4 - Strategies) 4. Specific Objectives and Goals T3CD has three main objectives: O.1) identify the major knowledge gaps that prevent an accurate assessment of celestial dust toxicity; O.2) propose standardized methodologies to estimate the inhalation health risk on celestial soil/dust using ground-based, low-gravity, and in situ measurements; O.3) participate in national and EU-funded competitive research projects 5. Duration/timeline of work The duration we are proposing is two years (April 1st 2019 - March 31st 2021). To achieve the project objectives defined in section 1.3, the following actions (A) will be implemented through teleconferences, in-person meetings and site visits. The T3CD will produce a number of deliverables (D), either directly delivered to ESA or to the broad Space scientific community. (see Annex 2 for further details) 4 6. Space Relevance and Justification for need of requested Topical Team In the next decade, Space agencies, including NASA and ESA, are planning to (re)start crewed missions toward the Moon and on to Mars. Future missions will allow scientists to learn more about the resources and hazards for humans beyond Low-Earth-Orbit (LEO) and will advance broader scientific questions related to the history of the Solar System and the emergence and co-evolution of life on Earth. Ultimately, crewed missions will provide information about the ability of humans to work and live in extreme environments. Crew members can be directly exposed to celestial dust in several ways, including: i) extravehicular activities (EVAs), they may introduce into the habitat dust from space suits and boots; ii) cleaning suits between EVAs and changing of the Environmental Control Life Support System filters; iii) returning to microgravity, the dust that is introduced into the return vehicle will “float” thus increasing the opportunity for ocular and respiratory injury. In the context of a bio-sustainable planetary exploration, the determination of the potential toxicity of celestial soils and dusts is a key element enabling human survival. However, the formation, composition and physical properties of celestial dusts (CD), including exposure routes, activation and passivation processes, are only partially investigated. Many key issues related to the interaction of celestial dusts with biological tissue and cells are largely unexplored, including the effect of microgravity on dust pulmonary cut-offs, the health effect of surface molecular species, the activation/deactivation kinetics of UV and solar wind exposed particles. (see Annex 2 for further details) 5 Annex 1. Short Biographical Sketches of all Team Members: Francesco Turci FT carries out research activities concerning the study of the physico-chemical properties of micro- and nanometric inorganic particulates, including silica, asbestos, and industrial powders, in relation to their toxicity. Within the activities of the "G. Scansetti" Center for Study on Asbestos and other Toxic Particulates, of which he is Deputy Director since 2015, FT coordinates the characterization facilities that include micro-Raman, micro-XRF spectroscopy, TGA-FTIR-GCMS thermal analysis, and nano and micrometric dimensional analysis with DLS / ELS and optical automated image analysis (details here). FT is co-author of more than 50 scientific publications on peer-reviewed journals in the field of particle and fiber e toxicology, 4 book chapters and 2 patents (https://orcid.org/0000-0002-5806-829X). He is currently involved in the following scientific research projects: ● "Surface silanols as Key Describer of the Silica Hazard - Experimental Validation", financing body: IMA - Eurosil, in collaboration with UCL, Brussels, role: PI ● "Application of the Rietveld Method in the Quantitative Determination of Asbestos in Complex Matrices", funding body: ARPA Valle d'Aosta, role: PI ● "SERS Biosensing with Nanoporous functionalized Gold" (BiNGo), University research projects 2014, funding body: Compagnia di San Paolo, role: WP coordinator ● "Amiante et Bonnes Pratiques" competitive research project funded by the CNRT (Center Nationale de Recherche Techonologique), Nouvelle-Calédonie, France ● "The streets of asbestos" MIUR Notice 6/2000 "Dissemination of Scientific Culture", role: participant ● "Use of irrigation water contaminated by asbestos: analysis of the risk related to dispersion, migration and aerodispersion of the fibers", Reg. Piemonte, Health Projects Finalized (36529 / DB2001), role: PI Erin Tranfield ET obtained her PhD studying the cardiovascular effects of particulate matter air pollution and her first post-doctoral fellowship was studying the toxicity effects of lunar dust at NASA Ames Research Center. Currently she is the head of the Electron Microscopy Facility at the Instituto Gulbenkian de Ciência just outside of Lisbon Portugal. ET applies her extensive knowledge of electron microscopy to projects ranging from the investigation of the influenza A virus infection on cell function, to the cellular changes of tissues associated with aging, to de novo structure development in plants. She is an active leader in several national initiatives for the establishment of a national cryo-EM research facility and consortiums for methods development for scientific research. She has been a member of the ESA Sponsored Topical Team on the Toxicity of Celestial Dusts since 2011. Wim van Westrenen WvW, professor of planetary evolution at Vrije Universiteit Amsterdam, is an experimental geochemist by training. He uses a combination of physical and chemical property measurements of extraterrestrial materials and remote sensing observations to study the internal differentiation and evolution of the Moon, Mars, Mercury, asteroids and rocky exoplanets. He has been involved in lunar science for the past 13 years. He uses a combination of information from high-pressure experiments and results from lunar missions to study the mineralogy and composition of the surface, crust, mantle and core of the Moon. His recent work focuses on the history and role of water in the interior of the Moon. He co-chaired ESA’s Topical Team on Exploitation of Local Planetary Materials (TT-ELPM) that focused in part on lunar volatiles, and coordinates the Netherlands membership to NASA’s Solar System Exploration Virtual Institute (SSERVI). Kim Prisk KP is a pulmonary physiologist with 40 years of experience in the field. He was the lead scientist on studies of pulmonary function in 5 flights of the Space Shuttle, worked with the ESA Life Sciences teams on both D-2 and STS-107, and flew a study of pulmonary function on the ISS (expeditions 3-6) in 2001-2003. In addition to the pulmonary function studies KP has extensive experience in aerosol transport and deposition in the human lung and the effects of gravity on those processes. These studies have involved many experiments performed in zero-G parabolic flight (over 3000 parabolas) and are the basis of much of our knowledge of the effects of gravity on aerosol deposition. KP has been an active collaborator with ESA since ~1990, and served as the chair of the oversight committee charged with ensuring proper scientific performance of the Pulmonary Function System used on ISS (a team which included the topical team member DL). KP is based at the University of California, San Diego and is active in the development and use of quantitative function MRI for studies of lung physiology. Urs Staufer USt is Professor for Micro and Nano Engineering at the Delft University of Technology studied experimental Solid-State Physics, Mathematics and Philosophy at the University of Basel, Switzerland, where he received his PhD summa cum laude in 1990. He started his activities on planetary exploration in 1998 with the development of an atomic force microscope [AFM] for the MECA payload on the Mars Mission ‘Surveyor 2001’, which was cancelled. He led the AFM experiment of the successor Mission ‘Phoenix’ of which he was Co-Investigator in 2008, and which produced the first extra-terrestrial particle size distribution in the clay and silt size range. Later, he participated in design studies of instruments for Lunar exploration and demonstrator experiments for using magnetic force microscopy for the detection of nano-phase iron particles. His broader research interest is in applying fundamental knowledge from nanoscience and microtechnology in scientific instrumentation, and advanced instrumentation for in-line material characterization and materialmodifications. Dag Linnarsson Dag Linnarsson MD PhD has been active as researcher in environmental physiology for 50 years mainly in diving, aviation and space physiology. He is Senior Professor of Baromedicine at Karolinska Institute, Stockholm, Sweden, and has been Principal Investigator for numerous space flight experiments on the US Space Shuttle, on the Russian Space station Mir and on the International Space station (ISS). On-going experiments on ISS focus on the pulmonary turnover of nitric oxide (NO) and its role for the diagnosis of airway inflammation in case of inhalation of toxic planetary dust. Other research areas have been the effects of artificial gravity as a countermeasure against orthostatic hypotension after spaceflight and the effects of gravity on the distributions of ventilation and perfusion in the lungs. Linnarsson has been advisor to ESA in many functions including membership of ESA’s Topical Team for the Toxicity of Celestial Dust. Per Gerde PG PhD, associate professor in inhalation toxicology at Karolinska Institutet. He is the inventor of the PreciseInhale inhalation exposure platform and founder of the company Inhalation Sciences Sweden AB that provides this technology to the market. His main research interest is inhalation pharmacokinetics and method development of small-scale aerosol exposure methods for use in translational research from cell cultures to human subjects. A main focus of the technology platform is to allow respirable aerosol testing of air pollutant particles or inhalation pharmaceuticals with high precision dosing and with minimum consumption of test material. Bice Fubini Dr. Bice Fubini has just retired from the University of Torino, Italy, where she was full professor of Chemistry. Her main research interest is the chemical basis of the toxicity of inhaled particles and fibers which she developed by promoting multidisciplinary studies and leading the “G. Scansetti” Interdepartmental Center for Studies on Asbestos and other Toxic Particulates, which coordinates research and formation activities in a large spectrum of departments, from earth sciences to occupational medicine. As president of the center she still follows several research projects in the field. She took part to various “consensus workshops” and served in working groups at the International Agency for Research on Cancer; JRC European Centre for the Validation of Alternative Methods; International Sciences Institute (US); Institut de Recherches sur la Sécurité (F); Environmental Protection Agency US, ANSES, Agence nationale de sécurité sanitaire, de l’alimentation d l’environnement et du travail (F). Lena Palmberg Lena Palmberg, MD is a Professor in Toxicology at Karolinska Institutet. The long term goal with her research is to lay the foundation for effective, future treatments through better understanding of the mechanisms behind chronic bronchitis and COPD (Chronic Obstructive Pulmonary Disease). Her research is also providing new knowledge on environmental factors that cause these diseases including exposure to particles/nanoparticles. She has developed advanced multicellular lung mucosa models including human primary cells as an important tool in her research. Lars Karlsson LK, MSc PhD, is a senior researcher and group leader of the Environmental Physiology Group at Karolinska Institutet Stockholm, Sweden. Currently, he is the PI for a large ongoing experiment on ISS that evaluate the pulmonary turnover of the biomarker nitric oxide and its role for the diagnosis of airway inflammation in case of inhalation of toxic planetary dust. This ongoing work on lung function in reduced gravity and in reduced atmospheric pressure mimics conditions that will prevail during future celestial exploration. LK has a background in both medicine and engineering with experience of both the physiological effects of altered gravity and ambient pressure as well as in technical and scientific management of medical research at the European Space Agency. LK is advisor in the ESA’s Topical Team for the Toxicity of Celestial Dust. David J. Loftus Dr. Loftus is a principal investigator and Medical Officer at NASA Ames, affiliated with both the Space Biosciences Division and the Center for Nanotechnology. The theme of Dr. Loftus’ research group is the interaction of novel materials with biological systems, ranging from nanotechnology to planetary materials. Dr. Loftus brings expertise in the scientific disciplines of biophysics, cell biology, biochemistry and materials science, and Dr. Loftus holds a Ph.D. in molecular biology. Dr. Loftus is a fully trained physician (M.D.), and is board qualified/certified in internal medicine and hematology. Dr. Loftus has extensive experience in performing both animal studies and in vitro biological tests. Dr. Loftus is the co-inventor of LunaChem, a compact instrument designed to measure the chemical reactivity of lunar dust, proposed to be delivered to the surface of the Moon. Dr. Loftus holds the record for the most technology inventions by a life scientist at NASA Ames. Dr. Loftus has lead successful animal and human research protocols, at both Stanford University and NASA Ames. He brings highly relevant experience from the NASA-sponsored study of lunar dust toxicity, and a wealth of relevant experience from a broad range of biomedical disciplines. Topical Team on the Toxicity of Celestial Dusts (T3CD) Name and full contact details of the team coordinator: Francesco Turci University of Torino Department of Chemistry Via P. Giuria, 7 I-10125 – Torino, Italy francesco.turci@unito.it Office: +39 011 670 7566 Mobile: +39 348 573 4293 ESA bidder code of Università degli Studi di Torino: 1000001029 Name and full contact details of the team members Erin Tranfield (co-coordinator) Dag Linnarsson (past coordinator) Urs Staufer Per Gerde David J. Loftus Kim Prisk Instituto Gulbenkian de Ciência Rua da Quinta Grande, 6 2780-156 Oeiras, Portugal Tel: +351 21 446 4691 etranfield@igc.gulbenkian.pt Karolinska Institutet Dept of Physiology and Pharmacology Biomedicum Q6 Solnavägen 9 171 77 Stockholm +46 70 594 4401 Dag.Linnarsson@ki.se Delft University of Technology Dept. of Precision and Microsystems Engineering Faculty of 3mE, Mekelweg 2, 2628 CD, Delft, The Netherlands. Tel: + 31 15 2786804 u.staufer@tudelft.nl Karolinska Institutet Institute of Environmental Medicine (IMM), Experimental asthma and allergy research, Imm/Eaaf Solnavägen 9, Kvarter 5b 171 65 Solna , Sweden Per.Gerde@ki.se NASA Ames Research Center Moffett Field, CA 94035, United States david.j.loftus@nasa.gov University of California, San Diego Department of Medicine 9500 Gilman Drive La Jolla, CA 92093-0852 USA +1-858-534-3233 kprisk@ucsd.edu Bice Fubini Lena Palmberg Lars Karlsson Wim van Westrenen University of Torino Department of Chemistry via P. Giuria 7, I-10125 -Torino, Italy bice.fubini@unito.it Karolinska Institutet Institute of Environmental Medicine (IMM), C6 Nobelsväg 13, 17177 Stockholm, Sweden Lena.Palmberg@ki.se +46 (0) 8-524 822 10 Karolinska Institutet Dept of Physiology and Pharmacology Solna Vägen 9, B5 171 77 Solna, Sweden Lars.Karlsson@ki.se +46 (0) 8-524 868 90 Department of Earth Sciences Faculty of Science Vrije Universiteit Amsterdam De Boelelaan 1085 1081 HV Amsterdam, Netherlands w.van.westrenen@vu.nl Abstract The Topical Team on the Toxicity of Celestial Dusts (T3CD) is composed by 11 well-respected scientists, carrying out research in a wide-ranging spectrum of disciplines. Holding a broad range of complementary skills and expertises, team members are able to address the most challenging questions in dust effects on human health. The team works in close contact with the ESA Human Space Exploration. T3CD aims to: O.1: identify the major knowledge gaps about celestial dust toxicity; O.2: propose standardized methodologies to estimate the inhalation health risk of celestial soil/dust; O.3: participate to research projects The objectives will be achieved through the following actions: A.1: Survey of activities on celestial dusts A.2: Propose standards methods for the handling, activation, passivation/inactivation kinetics, and curation of celestial dust analogues. A.3: Write CORA proposal A.4: Propose preliminary experiments for assessment of celestial dust toxicity A.5: Participate to calls A.6: Prepare attendance at conferences and workshops A.7: Prepare Roadmap Within the next two year funding cycle, this topical team will deliver: D.1: Critical review of scientific activities on CD D.2: Internal report of standards for toxicity of CD investigation D.3: Projects under CORA D.4: Report with experimental ideas D.5: Project proposal(s) D.6: Report about workshop/conference(s) D.7: Roadmap integration Periodic in-person meetings and conference calls will foster the achievement of project goals and circulate ideas through the team members. Primary project costs are meetings reimburses and participation to conferences and workshops. Keywords Human exploration, health effects, celestial dust, extraterrestrial soil, particle toxicology, inflammation, surface reactivity, Moon, Mars 1. Project Description 1.1 Vision In the next decade, Space agencies, including NASA and ESA, are planning to (re)start crewed missions toward the Moon and on to Mars. Future missions will allow scientists to learn more about the resources and hazards for humans beyond Low-Earth-Orbit (LEO) and will advance broader scientific questions related to the history of the Solar System and the emergence and co-evolution of life on Earth. Ultimately, crewed missions will provide information about the ability of humans to work and live in extreme environments. Crew members can be directly exposed to celestial dust in several ways, including: i) extravehicular activities (EVAs), they may introduce into the habitat dust from space suits and boots; ii) cleaning suits between EVAs and changing of the Environmental Control Life Support System filters; iii) returning to microgravity, the dust that is introduced into the return vehicle will “float” thus increasing the opportunity for ocular and respiratory injury. In the context of a bio-sustainable planetary exploration, the determination of the potential toxicity of celestial soils and dusts is a key element enabling human survival. However, the formation, composition and physical properties of celestial dusts (CD), including exposure routes, activation and passivation processes, are only partially investigated. Many key issues related to the interaction of celestial dusts with biological tissue and cells are largely unexplored, including the effect of microgravity on dust pulmonary cut-offs, the health effect of surface molecular species, the activation/deactivation kinetics of UV and solar wind exposed particles. This Topical Team will report about the toxicity of celestial dusts, especially with exposure resulting from dust inhalation. Human inhalation will be our primary focus because this is the most likely pathway for exposure that has the potential for significant toxicity concerns. Nonetheless, skin sensitization following abrasion, ocular and mouth mucosa damage, and general interaction of the dust with all kinds of Earthly life required for space survival (plants first, but also livestock) will be our concern. The members of this proposed team are well-respected scientists in a broad spectrum of disciplines from geology to medicine, through physics and engineering, chemistry, and biochemistry. Taken together, they hold a broad range of complementary skills and expertise able to address the most challenging questions in dust effects on human health. The team will work in close contact with the ESA Human Space Exploration working group. 1.2 Mission With a composition of international scientists holding a broad range of complementary skills and expertise in dust effects on human health, the Topical Team on the Toxicity of Celestial Dust (T3CD) provides ESA with scientific and technical advances in addressing the gaps in the scientific knowledge about features of the celestial dust and its toxicity. By filling such gaps, we provide scientifically based possibilities for mitigating the exposure of astronauts to potentially noxious dusts during planetary explorations and allow ESA to establish safe exposure limits. Habitats and vehicles shall be designed so that exposures of crews to celestial dusts would be limited to safe levels. 1.3 Objectives T3CD has three main objectives: O.1) identify the major knowledge gaps that prevent an accurate assessment of celestial dust toxicity; O.2) propose standardized methodologies to estimate the inhalation health risk on celestial soil/dust using ground-based, low-gravity, and in situ measurements; O.3) participate in national and EU-funded competitive research projects 1.4 Strategies We will accomplish these objectives through the following strategies: Meetings Prior experience has shown that the face-to-face meetings of the team are the most productive means of finalizing deliverables and shaping the future activities of the team. As such we propose that the team meets face-to-face at approximately 6-monthly intervals (2 meetings per year). Such meetings are the primary cost of the team collaboration but they are also highly productive periods that are critical to the forward progression of the action items. The meetings will be hosted at the institutes of the team members, as a way of reducing the costs of the meetings. This will also give us the opportunity to visit host laboratories to foster exchange of protocols and best practice. The team will also meet via teleconference calls on a regular basis to prepare general discussion and coordinate ongoing initiatives. Meeting Tentative number date Host/Location Meeting agenda M1 Spring 2019 University of Torino Turin, Italy ● Kick-off meeting (new members’ introduction) ● Samples and work-packages definition for CORA proposal ● Prepare of the draft scheme for the Critical Review (D.1) ● Discuss Funding opportunities (D.5) ● Select conference(s) for D.6-1 M2 Fall 2019 Karolinska Institute Stockholm, Sweden ● Feedback from ESA about Critical Review ● Define standard methodologies to investigate for D.2 ● Prepare provisional table of contents of Roadmap D.7 ● Discuss Funding opportunities (D.5) M3 Spring 2020 To Be Defined ● Finalize report on standard methodologies (D.2) ● Evaluate to-do list and distribute task for the Roadmap (D.7) ● Select conference(s) for D.6-2 ● Discuss Funding opportunities (D.5) M4 Fall 2020 To Be Defined ● Mid-term assessment on Roadmap. Evaluate remaining work and distribute task. ● Discuss Funding opportunities (D.5) ● Select conference(s) for D.6-3 ● Discuss about renewal to the T3CD project M5 Spring 2021 To Be Defined ● Finalize Roadmap (D.7) ● Discuss Funding opportunities (D.5) ● Decision about T3CD renewal / termination Participation to Local and European Calls Several years ago, this TT submitted a proposal to the FP-7 framework opportunity. This proposal sought to address the toxicity of lunar dust with specific emphasis on the reactivation of the (presumed lost) surface chemical activity of the dust. This proposal, although not funded, received excellent reviews. Since that time, we have refined and better focused our open questions and we plan to submit a revised proposal for the next Framework opportunity (FP-9, Horizon Europe). As part of this expectation and the refinement of our ideas, we have proposed to include the airlifted particulate deposition on cell cultures grown in TransWell chambers. This has led to the proposed inclusion of Dr Lena Palmberg from Karolinska Institutet as a new team member as she is an expert in this approach. It is planned that the team will continue to refine our ideas and submit a refined and better-focused proposal to examine both Lunar and Martian dust simulants using chemical and cellular responses. In addition, we are in the process of providing a response to the ESA Roadmap n° 8. That includes Recommendation for Heracles project specifically meant to describe requirements to properly collect samples within the Lunar Surface Science - Lander connected to the Deep Space Gateway project. We will prepare a response for the ALINA aspect of this initiative for proposed instruments to be placed on a Lunar Lander with an instrument that will give us both in-situ size distributions of Lunar Dust, and a limited chemical assay of the chemical reactivity of that dust though an innovative hydrogel patch approach. Interaction with SME The team is engaged in researches that will lead to the development of monitoring devices comparable to dosimeter for radiation. These dust-monitoring devices will need to be fabricated in small amounts and a market for the SMEs involved in the projects will be generated. Such monitoring devices are critical and, hence, cannot depend on a single source. Preliminary Experimental Work The team will engage in limited and specific experimental work to gain preliminary findings to fuel future research. Specifically we will: ● ● define and secure Lunar and Mars analogue dusts from US and European space agencies extend to Mars analogue samples the use of terephthalate assay (TA) successfully used to measure surface radical reactivity of Lunar dust analogue in aqueous media ● ● use the patented PreciseInhale platform to deliver Lunar- and Mars analogues to respiratory cells, cultured at the air/liquid interface include human primary lung epithelial cells in these tests using the TransWell system. The aim of these preliminary experiments will be to advance the current scientific understanding in these key areas providing added scientific strength to the recommendations of the team. These small experiments will generate preliminary data to support much larger proposals for experimental investigations (for example the upcoming FP-9, Horizon Europe call). Ground based facility (CORA programme call) As part of the development of the necessary infrastructure and fostering the capabilities that would benefit a Horizon Europe proposal, the team plans to respond via the CORA mechanism. This will allow the emergence of a clearer picture of how to approach questions surrounding the toxicity of celestial dusts. In this context it is important to understand that much progress can likely be achieved through the use of dust simulants, both for Mars and the Moon. Such an approach lends itself to activities under the CORA framework. The team is already active in defining the simulants to be used for both Lunar and Martian toxicity studies. A common approach will likely include the grinding (ball milling) of such simulants to produce dust samples of a size range comparable to that known to exist in the relevant environments. Such a process will serve to enhance surface chemical reactivity for the Lunar simulant. In the case of the Martian simulant, the plans include the intent to study the effects of perchlorate addition to the simulant, as perchlorate is a known component of the Martian surface with (at present) unknown toxicity effects in the context of inhaled exposure. 2. Action plan and deliverables The duration we are proposing is two years (April 1st 2019 - March 31st 2021). To achieve the project objectives defined in section 1.3, the following actions (A) will be implemented through teleconferences, inperson meetings, and site visits. The T3CD will produce a number of deliverables (D), either directly delivered to ESA or to the broad Space scientific community. A.1) Critically review the past and ongoing scientific activities on dust toxicity on Earth relevant to the toxicological evaluation of celestial soils and dusts. D.1: Report to ESA A.2) Propose standards for the handling, activation methods, passivation/inactivation kinetics, and curation of celestial dust analogues. D.2: Expose and discuss at workshops/conferences (under A.7) and report to ESA A.3) Prepare CORA Proposal(s). The T3CD members will engage in the participation to the CORA programme of ESA to submit proposal(s) about experiments required to gain a clearer picture of how to approach questions surrounding the toxicity of celestial dusts. Importantly, much progress can be achieved through the use of dust simulants, both for Mars and the Moon. Such an approach lends itself to activities under the CORA framework. D.3: Project under CORA to ESA A.4) Propose to ESA experimental ideas for celestial samples in the event of a sample return mission. D.4: Report to ESA with the experimental ideas A.5) Respond to RFI from ESA and participate in calls for Enabling Technology for Lunar Surface Science, including deployment of science packages for obtaining the desired measurements to provide long-term monitoring of the surface and subsurface environments for fundamental lunar science and crew safety. For example, the previous topical team sent a response ‘INSTALD’ to the RFI 09112018 of ESA proposing a Lunar surface experiment package. D.5: Project proposal(s) (dates are TBD and will be based on call dates) A.6) Attendance at ESA workshops and Space scientific conferences. The T3CD members shall attend to joint workshop with other TTs. D.7: presentation of T3CD work (dates are TBD and will be based on conference dates) A.7) Preparation of a Roadmap towards a safe human space exploration. The TT will develop a roadmap integration for making human space exploration safe in terms of exposure to celestial dust. The group attention will be focused also on the fundamental question of life sustainability, including plants and livestock. This traces and links the three fundamental phases outlined in Figure 1 (‘Vision’): Phase 1: Assessment of the toxicity and acceptable levels of exposure, Phase 2: Definition of monitoring procedures and countermeasures against exposure, decontamination procedures; and Phase 3: Development of monitoring equipment and support of human space exploration. The roadmap will be a working document regularly updated and shared with funding agencies and decision bodies. It shall help steer the research in the field of dust toxicity. The roadmap will includes recommendations for the Heracles Project specifically meant to describe requirements to properly collect samples within the Lunar Surface Science - Lander connected to the Deep Space Gateway project. D.8: Roadmap integration to ESA