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Emerging epidemiological data suggest that early-life exposure to metals and metal mixtures is associated with altered fetal and child growth, but underlying modes of action (MoAs) are largely unknown. The overall purpose of this 4-year project is to delineate underlying mechanisms of metal mixture toxicity by targeted and non-targeted approaches, combining data from a Swedish birth cohort (n=600) with an established developmental toxicity model. Metal mixtures (cadmium, lead, methylmercury, fluoride) have been measured during pregnancy, and in the children at 4 months and 4 years using well-established exposure biomarkers. These measurements will be related to several growth/bone-related hormones and bone remodeling markers at 4 years using statistical models designed for mixtures [Weighted Quantile Sum regression (WQS) and Bayesian Kernel Machine Regression (BKMR)]. In parallel, we will study morphological, functional and molecular effects of the metal’s mixtures on zebrafish development and growth, combining a targeted (morphometrics, hormone levels) and untargeted approach (RNAseq, metabolomics). Altogether, this will increase our understanding of MoAs for metal-induced adverse effects on child growth and critical windows of exposure, enable us to identify novel molecular markers for key events in these MoAs, and thereby strengthen causality in epidemiological data, all which can serve as tools for future health risk monitoring and preventive actions.

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.