italy is currently one of the countries seriously affected by the coVid-19 pandemic. as per 10 april 2020, 147,577 people were found positive in a total of 906,864 tests performed and 18,849 people lost their lives. among all cases, 70.2% of positive, and 79.4% of deaths occurred in the provinces of northern italy (lombardi, emilia romagna, Veneto and Piemonte), where the outbreak first started. Originally, it was considered that the high number of positive cases and deaths in italy resulted from coVid-19 initially coming to italy from china, its presumed country of origin. However, an analysis of the factors that played a role in the extent of this outbreak is needed. Evaluating which factors could be specific for a country and which might contribute the most is nevertheless complex, with accompanying high uncertainty. The purpose of this work is to discuss some of the possible contributing factors and their possible role in the relatively high infection and death rates in northern italy compared to other areas and countries.

Multiple medical, lifestyle, and environmental conditions, including smoking and particulate pollution, have been considered as risk factors for CO rona VI rus D isease 2019 (COVID-19) susceptibility and severity. Taking into account the high level of toxic metals in both particulate matter (PM2.5) and tobacco smoke, the objective of this review is to discuss recent data on the role of heavy metal exposure in development of respiratory dysfunction, immunotoxicity, and severity of viral diseases in epidemiological and experimental studies, as to demonstrate the potential crossroads between heavy metal exposure and COVID-19 severity risk. The existing data demonstrate that As, Cd, Hg, and Pb exposure is associated with respiratory dysfunction and respiratory diseases (COPD, bronchitis). These observations corroborate laboratory findings on the role of heavy metal exposure in impaired mucociliary clearance, reduced barrier function, airway inflammation, oxidative stress, and apoptosis. The association between heavy metal exposure and severity of viral diseases, including influenza and respiratory syncytial virus has been also demonstrated. The latter may be considered a consequence of adverse effects of metal exposure on adaptive immunity. Therefore, reduction of toxic metal exposure may be considered as a potential tool for reducing susceptibility and severity of viral diseases affecting the respiratory system, including COVID-19.

Human biomonitoring has become a pivotal tool for supporting chemicals’ policies. It provides information on real-life human exposures and is increasingly used to prioritize chemicals of health concern and to evaluate the success of chemical policies. Europe has launched the ambitious REACH program in 2007 to improve the protection of human health and the environment. In October 2020 the EU commission published its new chemicals strategy for sustainability towards a toxic-free environment. The European Parliament called upon the commission to collect human biomonitoring data to support chemical’s risk assessment and risk management. This manuscript describes the organization of the first HBM4EU-aligned studies that obtain comparable human biomonitoring (HBM) data of European citizens to monitor their internal exposure to environmental chemicals. The HBM4EU-aligned studies build on existing HBM capacity in Europe by aligning national or regional HBM studies. The HBM4EU-aligned studies focus on three age groups: children, teenagers, and adults. The participants are recruited between 2014 and 2021 in 11 to 12 primary sampling units that are geographically distributed across Europe. Urine samples are collected in all age groups, and blood samples are collected in children and teenagers. Auxiliary information on socio-demographics, lifestyle, health status, environment, and diet is collected using questionnaires. In total, biological samples from 3137 children aged 6–12 years are collected for the analysis of biomarkers for phthalates, HEXAMOLL® DINCH, and flame retardants. Samples from 2950 teenagers aged 12–18 years are collected for the analysis of biomarkers for phthalates, Hexamoll® DINCH, and per- and polyfluoroalkyl substances (PFASs), and samples from 3522 adults aged 20–39 years are collected for the analysis of cadmium, bisphenols, and metabolites of polyaromatic hydrocarbons (PAHs). The children’s group consists of 50.4% boys and 49.5% girls, of which 44.1% live in cities, 29.0% live in towns/suburbs, and 26.8% live in rural areas. The teenagers’ group includes 50.6% girls and 49.4% boys, with 37.7% of residents in cities, 31.2% in towns/suburbs, and 30.2% in rural areas. The adult group consists of 52.6% women and 47.4% men, 71.9% live in cities, 14.2% in towns/suburbs, and only 13.4% live in rural areas. The study population approaches the characteristics of the general European population based on age-matched EUROSTAT EU-28, 2017 data; however, individuals who obtained no to lower educational level (ISCED 0–2) are underrepresented. The data on internal human exposure to priority chemicals from this unique cohort will provide a baseline for Europe’s strategy towards a non-toxic environment and challenges and recommendations to improve the sampling frame for future EU-wide HBM surveys are discussed.

Research over the past years has indicated that chronic human exposure to very low doses of various chemical species in mixtures and administered via different routes (percutaneous, orally, etc.) should be the main focus of new biochemical and toxicological studies. Humans have daily contact with various chemicals, such as food additives, pesticides from fruits/vegetables, antibiotics (and other veterinary drugs) from meat, different types of preservatives from cosmetics, to name a few. Simultaneous exposure to this wide array of chemicals does not produce immediate effects, but summative effect/s over time that may be clinically manifested several years thereafter. Classical animal studies designed to test the toxic outcome of a single chemical are not suitable to assess, and then extrapolate to humans, the effects of a whole mixture of chemicals. Testing the aftermath of a combination of chemicals, at low doses, around or below the no observed adverse effect is stressed by many toxicologists. Thus, there is a need to reformulate the design of biochemical and toxicological studies in order to perform real-life risk simulation. This review discuss the potential use of computational methods as a complementary tool for in vitro and in vivo toxicity tests with a high predictive potential that could contribute to reduce animal testing, cost and time, when assessing the effects of chemical combinations. This review focused on the use of these methods to predict the potential endocrine disrupting activity of a mixture of chemicals. Contents 1. The need for a change in the current scientific paradigm 2. Relevance of exposure to mixtures of endocrine disruptor chemicals in the context of 21st century research 3. Future directions in real-life risk simulations of endocrine disruptors 4. Conclusions 1. The need for a change in the current scientific paradigm Human populations come into contact, on a daily basis, with a large range of chemical mixtures, at low levels of exposure, from virtually every product that is used, from the food consumed (raw or processed, either vegetal, containing soil originating substances, or animal), drinking water (tap or bottled), the air