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Research problem and specific questions: Cleaning and disinfection agents are widely used in various occupational settings and a growing body of evidence from observational studies shows this results in lung function impairments. However, mechanisms a behind these effects are yet unclear. This project aims to clarify the risks of lung disease posed by the mixtures in cleaning agents and evaluate the adequacy of applicable regulations. Specifically:Which biomarkers of cell membrane integrity inflammation, toxicity and cell death are activated in in vitro advanced lung mucosa models by cleaning agent exposure?How do responses compare between alveolar and bronchial mucosa models?How do responses compare between exposures to mixtures and ingredients one by one?What are the implications of potential mixture effects for regulatory hazard assessments?Data and method: We will employ systematic literature search strategies and new approach methodologies (NAMs), including advanced multicellular lung mucosa in vitro models and adverse outcome pathways (AOPs). The AOPs will be used to organise existing knowledge and translate experimental findings, such as molecular mechanisms and cellular reactions in vitro, to a human in vivo setting.Plan for project realisation: The project will start with a scoping review to connect mechanistic data to adverse respiratory tract outcomes and map out a tentative AOP network and identify mechanisms, or key events, of particular relevance to pursue experimentally. Next, experimental work on fully formulated products will be performed in multi-cellular human bronchial and alveolar models. To start untangling the mixture effects the third substudy concerns experimental work on single substance exposures. Finally, we will perform case-studies on mixture risk assessment inhalation exposure to cleaning agents.Relevance: The wide-spread use of cleaning agents makes it a chemical risk factor for a broad part of the workforce. A mechanistic understanding is essential for regulatory risk assessment, as are further studies of cleaning agents’ mixture effects and their role in lung disease. Our project is a step in identifying problematic substances and substance combinations in mixtures and lays the foundation for knowledge that can lead to reformulation of cleaning agents into safer alternatives. Our project also contributes to the field of mixture risk assessment, where inhalation exposure of mixtures is under-researched field.

INQUIRE aims to protect citizen health by providing knowledge, tools, and measures to substantially improve indoor air quality (IAQ). We will conduct research and evaluate innovative actions to reduce hazardous chemical and biological determinants in homes, positively impacting the health of residents. INQUIRE will focus particularly on infants and young children (<5 years old) as highly sensitive groups that spend a substantial time in the home environment. INQUIRE will comprehensively advance our understanding of the determinants of IAQ in homes by implementing innovative, low-cost, non-invasive sampling strategies (sensors, indoor/outdoor passive sampling, urine biomonitoring) to characterize determinants of household IAQ and their importance to human exposure. To capture the breath of IAQ determinants across Europe, the study will monitor for one month over 200 homes distributed across 8 countries, covering a gradient of conditions in each country. Tiered high-resolution chemical and biological screening techniques and wide-scope holistic characterisation of hazards will provide a comprehensive assessment of the determinants of IAQ. Multifaceted data analysis techniques (including machine learning, exposure modelling, geospatial analysis), will link chemical, biological and toxicity profiles with drivers of IAQ to identify sources and prioritize pollutants. Source identification will feed directly into the testing of both novel technologies and readily deployable strategies to improve IAQ, resulting in evidence-based recommendations and a draft of policy strategy for developing IAQ standards. INQUIREs Open Science approach and generated FAIR data on hazardous determinants, their effects, risk factors and sources will endorse continuous exploitation of results. Open dissemination of generated knowledge will raise citizen awareness while exploitation by industry and policy makers will endorse a transition towards homes with zero pollution. The project INQUIRE is part of the European cluster on indoor air quality and health, IDEAL.