Browsing Articles and other publications by RIVM employees by Submit Date
Now showing items 1-20 of 3908
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Long-term exposure to air pollution and mortality in a Danish nationwide administrative cohort study: Beyond mortality from cardiopulmonary disease and lung cancer.We followed all residents aged ≥ 30 years (3,083,227) in Denmark from 1 January 2000 until 31 December 2017. Annual mean concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), and ozone (warm season) were estimated using European-wide hybrid land-use regression models (100 m × 100 m) and assigned to baseline residential addresses. We used Cox proportional hazard models to evaluate the association between air pollution and mortality, accounting for demographic and socioeconomic factors. We additionally applied indirect adjustment for smoking and body mass index (BMI).
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A physiologically based pharmacokinetic model to predict pegylated liposomal doxorubicin disposition in rats and human.The use of nanoparticles (NPs) can support an enhancement of drug distribution, resulting in increased drug penetration into key tissues. Experimental in vitro data can be integrated into computational approaches to simulate NP absorption, distribution, metabolism and elimination (ADME) processes and provide quantitative pharmacokinetic predictions. The aim of this study is to develop a novel mechanistic and physiologically based pharmacokinetic (m-PBPK) model to predict the biodistribution of NPs focusing on Doxil. The main processes underpinning NPs ADME were represented considering molecular and cellular mechanisms such as stability in biological fluids, passive permeability and uptake activity by macrophages. A whole-body m-PBPK rat and human models were designed in Simbiology v. 9.6.0 (MATLAB R2019a). The m-PBPK models were successfully qualified across doxorubicin and Doxil® in both rat and human since all PK parameters AUC0-inf, Cmax, t1/2, Vd and Cl were within twofold, with an AUC0-inf absolute average-fold error (AAFE) value of 1.23 and 1.16 and 1.76 and 1.05 for Doxorubicin and Doxil® in rat and human, respectively. The time to maximum concentration in tissues for doxorubicin in both rat and human models was before 30 min of administration, while for Doxil®, the tmax was after 24 h of administration. The organs that accumulate most NP are the spleen, liver and lungs, in both models. The m-PBPK represents a predictive platform for the integration of in vitro and formulation parameters in a physiological context to quantitatively predict the NP biodistribution. Schematic diagram of the whole-body m-PBPK models developed for Doxil® in rat and human physiology.
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Photochemical degradation pathways of cell-free antibiotic resistance genes in water under simulated sunlight irradiation: Experimental and quantum chemical studies.The presence of antibiotic resistance genes (ARGs) in the environment poses a threat to human health and therefore their environmental behavior needs to be studied urgently. A systematic study was conducted on the photodegradation pathways of the cell-free tetracycline resistance gene (Tc-ARG) under simulated sunlight irradiation. The results showed that Tc-ARG can undergo direct photodegradation, which significantly reduces its horizontal transfer efficiency. Suwannee River fulvic acid (SRFA) promoted the photodegradation of Tc-ARG and further inhibited its horizontal transfer by generating reactive intermediates. The photodegradation of Tc-ARG was attributed to degradation of the four bases (G, C, A, T) and the deoxyribose group. Quantum chemical calculations showed that the four bases could be oxidized by the hydroxyl radical (HO) through addition and H-abstraction reactions. The main oxidative product 8-oxo-dG was detected. This product was generated through the addition reaction of G-C with HO, subsequent to dissolved oxygen initiated H-abstraction and H2O catalyzed H-transfer reactions. The predicted maximum photodegradation rates of Tc-ARG in the Yellow River estuary were 0.524, 0.937, and 0.336 h-1 in fresh water, estuary water, and seawater, respectively. This study furthermore revealed the microscopic photodegradation pathways and obtained essential degradation parameters of Tc-ARG in sunlit surface water.