Fine 2. Author names: Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 7 Given name: [Marija Sollner] Last name [Dolenc]. Also, kindly confirm the details in the metadata are correct.The given name is Marija, the last name is Sollner Dolenc.

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The development of new low molecular weight drugs has many chances of failure and is an expensive process. Currently, there are no screening methods and/or models to assess the hazard of hypersensitivity reactions to drugs (DHRs) in the preclinical phase. DHRs represent 6–15% of adverse drug reactions. Although rare, DHRs represent a serious health problem for predisposed individuals, resulting, in some cases, in life-threatening pathologies. To date, there are no in vitro or in vivo sensitive models able to predict the sensitizing potential of drugs in the preclinical tests, and these reactions are highlighted only after the drug has been placed on the market, affecting both population and public health. This article describes a novel approach methodology for the study of the sensitizing potential of drugs based on the use of the human promyelocytic cell line THP-1 as a surrogate for dendritic cells. The method is based on the upregulation of specific surface markers (CD86 and CD54) and on the production of IL-8. In our experience, the THP-1 activation assay allowed the correct identification of drugs known to induce systemic hypersensitivity in humans, including the one associated with specific HLAs. This method may help to discover possible systemic hypersensitivity reactions early in the preclinical phase of drug development.

The RHAPS (Redox-Activity And Health-Effects Of Atmospheric Primary And Secondary Aerosol) project was launched in 2019 with the major objective of identifying specific properties of the fine atmospheric aerosol from combustion sources that are responsible for toxicological effects and can be used as new metrics for health-related outdoor pollution studies. In this paper, we present the overall methodology of RHAPS and introduce the phenomenology and the first data observed. A comprehensive physico-chemical aerosol characterization has been achieved by means of high-time resolution measurements (e.g., number size distributions, refractory chemical components, elemental composition) and low-time resolution analyses (e.g., oxidative potential, toxicological assays, chemical composition). Preliminary results indicate that, at the real atmospheric conditions observed (i.e., daily PM1 from less than 4 to more than 50 μg m−3), high/low mass concentrations of PM1, as well as black carbon (BC) and water soluble Oxidative Potential (WSOP,) do not necessarily translate into high/low toxicity. Notably, these findings were observed during a variety of atmospheric conditions and aerosol properties and with different toxicological assessments. Findings suggest a higher complexity in the relations observed between atmospheric aerosol and toxicological endpoints that go beyond the currently used PM1 metrics. Finally, we provide an outlook to companion papers where data will be analyzed in more detail, with the focus on source apportionment of PM1 and the role of source emissions on aerosol toxicity, the OP as a predictive variable for PM1 toxicity, and the related role of SOA possessing redox-active capacity, exposure-response relationships for PM1, and air quality models to forecast PM1 toxicity.