The relevance of the food roduction chain with regard to the population exposure to chemical substances and its role in contaminated sites

Food may be contaminated with many chemical substances at any level along the production chain. Chemicals that may be found in food items can simultaneously be present in other matrices, as air, water, soil and dust; therefore, human exposure to chemicals via food has to be summed to the exposure through all the other possible routes. The role played by the food production chain with regard to the population exposure to chemicals assumes amplified proportions when considering contaminated sites. Indeed the link between environment and food production is undeniable and consequently, when population chemical exposure is considered, an integrated approach assessing the contribution of the different routes of exposure, including dietary exposure, is needed. Such integrated approach allows a realistic and comprehensive risk assessment of chemical substances in order to identify and deploy effective prevention and intervention measures to protect human health

A mouse mastitis model to study the effects of the intramammary infusion of a food-grade Lactococcus lactis strain

Lactococcus lactis is one of the most important microorganisms in the dairy industry and has "generally recognized as safe" (GRAS) status. L. lactis belongs to the group of lactic acid bacteria (LAB) and is encountered in a wide range of environments. Recently, the use of the intramammary infusion of a live culture of LAB has been investigated as a new antibiotic alternative for treating mastitis in dairy ruminants. Controversial results are described in literature regarding its efficacy and safety. In this study we conducted in-depth investigation of the mammary gland immune response induced by intramammary inoculum of a live culture of L. lactis LMG 7930 using the mouse mastitis model. Overnight cultures either of L. lactis (≈ 107 CFU) or of the mastitis pathogens Staphylococcus chromogenes (≈ 105 CFU) or S. aureus (≈ 102 CFU/ml) were injected into the mouse inguinal glands. A double injection, consisting of S. chromogenes first and then L. lactis, was also investigated. Bacterial recovery from the gland and inflammatory cell infiltration were assessed. L. lactis-treated and control glands were analysed for proinflammatory cytokine production. Microbiological results showed that L. lactis was able to survive in the mammary gland 24 h post infection, as were the mastitis pathogens S. chromogenes and S. aureus. L. lactis reduced S. chromogenes survival in the glands and increased its own survival ability by coexisting with the pathogen. Histology showed that L. lactis-treated glands presented variable histological features, ranging from undamaged tissue with no inflammatory cell infiltrate to severe PMN infiltrate with focal areas of tissue damage. S. aureus-treated glands showed the most severe histological grade of inflammation despite the fact that the inoculum size was the smallest. In contrast, most S. chromogenes-treated glands showed normal structures with no infiltration or lesions. Significant increases in IL-1β and TNF-α levels were also found in L. lactis-inoculated glands. The above findings seem to suggest that food-grade L. lactis at a high-inoculum dose such as an overnight culture may elicit a suppurative inflammatory response in the mammary gland, thus becoming a potential mastitis-causing pathogen. Because of the unpredictable potential of L. lactis in acting as a potential mastitis pathogen, this organism cannot be considered a safe treatment for bovine mastitis

Human-BasedNewApproachMethodologiesin DevelopmentalToxicityTesting:AStepAheadfromtheState oftheArtwithaFeto–PlacentalOrgan-on-ChipPlatform

Download PDFsettingsOrder Article Reprints Open AccessReview Human-Based New Approach Methodologies in Developmental Toxicity Testing: A Step Ahead from the State of the Art with a Feto–Placental Organ-on-Chip Platform by Michaela Luconi 1,2,†ORCID,Miguel A. Sogorb 3,†ORCID,Udo R. Markert 4ORCID,Emilio Benfenati 5,Tobias May 6,Susanne Wolbank 7ORCID,Alessandra Roncaglioni 5,Astrid Schmidt 4,Marco Straccia 8ORCID andSabrina Tait 9,*ORCID 1 Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy 2 I.N.B.B. (Istituto Nazionale Biostrutture e Biosistemi), Viale Medaglie d’Oro 305, 00136 Rome, Italy 3 Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Avenida de la Universidad s/n, 03202 Elche, Spain 4 Placenta Lab, Department of Obstetrics, University Hospital Jena, Am Klinikum 1, 07747 Jena, Germany 5 Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milan, Italy 6 InSCREENeX GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany 7 Ludwig Boltzmann Institut for Traumatology, The Research Center in Cooperation with AUVA, Austrian Cluster for Tissue Regeneration, Donaueschingenstrasse 13, 1200 Vienna, Austria 8 FRESCI by Science&Strategy SL, C/Roure Monjo 33, Vacarisses, 08233 Barcelona, Spain 9 Centre for Gender-Specific Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy * Author to whom correspondence should be addressed. † These authors contributed equally to this work. Int. J. Environ. Res. Public Health 2022, 19(23), 15828; https://doi.org/10.3390/ijerph192315828 Submission received: 24 October 2022 / Revised: 20 November 2022 / Accepted: 25 November 2022 / Published: 28 November 2022 (This article belongs to the Section Toxicology and Public Health) Downloadkeyboard_arrow_down Browse Figures Review Reports Versions Notes Abstract Developmental toxicity testing urgently requires the implementation of human-relevant new approach methodologies (NAMs) that better recapitulate the peculiar nature of human physiology during pregnancy, especially the placenta and the maternal/fetal interface, which represent a key stage for human lifelong health. Fit-for-purpose NAMs for the placental–fetal interface are desirable to improve the biological knowledge of environmental exposure at the molecular level and to reduce the high cost, time and ethical impact of animal studies. This article reviews the state of the art on the available in vitro (placental, fetal and amniotic cell-based systems) and in silico NAMs of human relevance for developmental toxicity testing purposes; in addition, we considered available Adverse Outcome Pathways related to developmental toxicity. The OECD TG 414 for the identification and assessment of deleterious effects of prenatal exposure to chemicals on developing organisms will be discussed to delineate the regulatory context and to better debate what is missing and needed in the context of the Developmental Origins of Health and Disease hypothesis to significantly improve this sector. Starting from this analysis, the development of a novel human feto–placental organ-on-chip platform will be introduced as an innovative future alternative tool for developmental toxicity testing, considering possible implementation and validation strategies to overcome the limitation of the current animal studies and NAMs available in regulatory toxicology and in the biomedical field

Italian Children Exposure to Bisphenol A: Biomonitoring Data from the LIFE PERSUADED Project

A human biomonitoring (HBM) study on bisphenol A (BPA) in Italian children and adolescents was performed within the LIFE PERSUADED project, considering the residing areas, sex and age. The median urinary BPA level was 7.02 mu g/L, with children living in the South of Italy or in urban areas having higher levels than those residing in the North or in rural areas. Children aged 4-6 years had higher BPA levels than those aged 7-10 and 11-14 years, but no differences were detected between sexes. The exposure in Italian children was higher compared to children from other countries, but lower than the HBM guidance value (135 mu g/L). The estimated daily intake was 0.17 mu g/kg body weight (bw) per day, about 24-fold below the temporary Tolerable Daily Intake of 4 mu g/kg bw per day established by the European Food Safety Authority. However, this threshold was exceeded in 1.44% of the enrolled children, raising concern about the overall exposure of Italian young population

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children