| 1. |
- Ali, Nadeem, et al.
(författare)
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Semi-Volatile Organic Compounds in Car Dust : A Pilot Study in Jeddah, Saudi Arabia
- 2021
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 18:9
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Tidskriftsartikel (refereegranskat)abstract
- People may spend a significant amount of their daily time in cars and thus be exposed to chemicals present in car dust. Various chemicals are emitted from during car use, contaminating the car dust. In this study, we compiled published and unpublished data on the occurrence of phthalates, flame retardants (FRs), polycyclic aromatic hydrocarbons (PAHs), and polychlorinated biphenyls (PCBs) in Saudi car dust. Phthalates, a class of chemical commonly used as plasticizers in different car parts, were the major pollutants found in car dust, with a median value of n-ary sumation phthalates 1,279,000 ng/g. Among other chemicals, organophosphate flame retardants (OPFRs) were found to be between 1500-90,500 ng/g, which indicates their use as alternative FRs in the car industry. The daily exposure to Saudi drivers (regular and taxi drivers) was below the respective reference dose (RfD) values of the individual chemicals. However, the estimated incremental lifetime cancer risk (ILCR) values due to chronic exposure to these chemicals was >1 x 10(-5) for taxi drivers for phthalates and PAHs, indicating that the long-term exposure to these chemicals is a cause of concern for drivers who spend considerable time in cars. The study has some limitations, due to the small number of samples, lack of updated RfD values, and missing cancer slope factors for many studied chemicals. Despite these limitations, this study indicates the possible range of exposure to drivers from chemicals in car dust and warrants further extensive studies to confirm these patterns.
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| 2. |
- Mann, Stefan A., et al.
(författare)
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Convergence of models of human ventricular myocyte electrophysiology after global optimization to recapitulate clinical long QT phenotypes
- 2016
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Ingår i: Journal of Molecular and Cellular Cardiology. - : Elsevier BV. - 0022-2828 .- 1095-8584. ; 100, s. 25-34
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Tidskriftsartikel (refereegranskat)abstract
- In-silico models of human cardiac electrophysiology are now being considered for prediction of cardiotoxicity as part of the preclinical assessment phase of all new drugs. We ask the question whether any of the available models are actually fit for this purpose. We tested three models of the human ventricular action potential, the O'hara-Rudy (ORD11), the Grandi-Bers (GB10) and the Ten Tusscher (TT06) models. We extracted clinical QT data for LQTS1 and LQTS2 patients with nonsense mutations that would be predicted to cause 50% loss of function in I-Ks and I-Kr respectively. We also obtained clinical QT data for LQTS3 patients. We then used a global optimization approach to improve the existing in silico models so that they reproduced all three clinical data sets more closely. We also examined the effects of adrenergic stimulation in the different LQTS subsets. All models, in their original form, produce markedly different and unrealistic predictions of QT prolongation for LQTS1, 2 and 3. After global optimization of the maximum conductances for membrane channels, all models have similar current densities during the action potential, despite differences in kinetic properties of the channels in the different models, and more closely reproduce the prolongation of repolarization seen in all LQTS subtypes. In-silico models of cardiac electrophysiology have the potential to be tremendously useful in complementing traditional preclinical drug testing studies. However, our results demonstrate they should be carefully validated and optimized to clinical data before they can be used for this purpose.
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