Deliverable 9.1 - Report on mixtures and implementation strategy in Europe – Assessment of chemical mixtures under consideration of current and future regulatory requirements and scientific approaches

This report gives an overview on the regulatory processes and requirements for risk assessment of chemical mixtures, identifies gaps in the European legislation and summarises potential approaches for the health risk assessment of chemical mixtures

Self-aligning planarization and passivation for integration applications in III-V semiconductor devices

Cataloged from PDF version of article.This paper reports an easy planarization and passivation approach for the integration of III-V semiconductor devices. Vertically etched III-V semiconductor devices typically require sidewall passivation to suppress leakage currents and planarization of the passivation material for metal interconnection and device integration. It is, however, challenging to planarize all devices at once. This technique offers wafer-scale passivation and planarization that is automatically leveled to the device top in the 1-3-mum vicinity surrounding each device. In this method, a dielectric hard mask is used to define the device area. An undercut structure is intentionally created below the hard mask, which is retained during the subsequent polymer spinning and anisotropic polymer etch back., The spin-on polymer that fills in the undercut seals the sidewalls for all the devices across the wafer. After the polymer etch back, the dielectric mask is removed leaving the polymer surrounding each device level with its device top to atomic scale flatness. This integration method is robust and is insensitive to spin-on polymer thickness, polymer etch nonuniformity, and device height difference. It prevents the polymer under the hard mask from etch-induced damage and creates a polymer-free device surface for metallization upon removal of the dielectric mask. We applied this integration technique in fabricating an InP-based photonic switch that consists of a mesa photodiode and a quantum-well waveguide modulator using benzocyclobutene (BCB) polymer. We demonstrated functional integrated photonic switches with high process yield of >90%, high breakdown voltage of >25 V, and low ohmic contact resistance of similar to 10 Omega. To the best of our knowledge, such an integration of a surface-normal photodiode and a lumped electroabsorption modulator with the use of BCB is the first to be implemented on a single substrate

Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife.

An expert meeting was organized by the World Health Organization (WHO) and held in Stockholm on 15-18 June 1997. The objective of this meeting was to derive consensus toxic equivalency factors (TEFs) for polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and dioxinlike polychlorinated biphenyls (PCBs) for both human, fish, and wildlife risk assessment. Based on existing literature data, TEFs were (re)evaluated and either revised (mammals) or established (fish and birds). A few mammalian WHO-TEFs were revised, including 1,2,3,7,8-pentachlorinated DD, octachlorinated DD, octachlorinated DF, and PCB 77. These mammalian TEFs are also considered applicable for humans and wild mammalian species. Furthermore, it was concluded that there was insufficient in vivo evidence to continue the use of TEFs for some di-ortho PCBs, as suggested earlier by Ahlborg et al. [Chemosphere 28:1049-1067 (1994)]. In addition, TEFs for fish and birds were determined. The WHO working group attempted to harmonize TEFs across different taxa to the extent possible. However, total synchronization of TEFs was not feasible, as there were orders of a magnitude difference in TEFs between taxa for some compounds. In this respect, the absent or very low response of fish to mono-ortho PCBs is most noticeable compared to mammals and birds. Uncertainties that could compromise the TEF concept were also reviewed, including nonadditive interactions, differences in shape of the dose-response curve, and species responsiveness. In spite of these uncertainties, it was concluded that the TEF concept is still the most plausible and feasible approach for risk assessment of halogenated aromatic hydrocarbons with dioxinlike properties

Overview on legislation and scientific approaches for risk assessment of combined exposure to multiple chemicals: the potential EuroMix contribution

This article reviews the current legislative requirements for risk assessment of combined exposure to multiple chemicals via multiple exposure routes, focusing on human health and particularly on food-related chemicals. The aim is to identify regulatory needs and current approaches for this type of risk assessment as well as challenges of the implementation of appropriate and harmonized guidance at international level. It provides an overview of the current legal requirements in the European Union (EU), the United States and Canada. Substantial differences were identified in the legal requirements for risk assessment of combined exposure to multiple chemicals and its implementation between EU and non-EU countries and across several regulatory sectors. Frameworks currently proposed and in use for assessing risks from combined exposure to multiple chemicals via multiple routes and different durations of exposure are summarized. In order to avoid significant discrepancies between regulatory sectors or countries, the approach for assessing risks of combined exposure should be based on similar principles for all types of chemicals. OECD and EFSA identified the development of harmonized methodologies for combined exposure to multiple chemicals as a key priority area. The Horizon 2020 project “EuroMix” aims to contribute to the further development of internationally harmonized approaches for such risk assessments by the development of an integrated test strategy using in vitro and in silico tests verified for chemical mixtures based on more appropriate data on potential combined effects. These approaches and testing strategies should be integrated in a scientifically based weight of evidence approach to account for complexity and uncertainty, to improve risk assessment

Woodrow Wilson’s diplomatic agenda and strategic military interventions: how they affected the Russian Civil War 1918-1920

This thesis aims to understand the factors that affected Woodrow Wilson’s foreign and military policy actions, which subsequently led to decisions that dictated United States’ intervention into the Russian Civil War, 1918-1920. The background information discussed demonstrates the importance of the Russian Civil War. This chaotic time in history surrounding World War I caused much of Woodrow Wilson’s dilemma and consequentially changed future of Soviet-American relations. It details how it would take numerous foreign policy shifts to convince Mr. Wilson to send U.S. troops to intervene into North Russia and Siberia. Lenin’s opposing perspective will encompass what is contained in much of the supporting information surrounding this thesis. In conjunction with military operations there, the allies attempted to broker peace with Lenin and the Bolsheviks in the form of the Prinkipo Proposal, the Bullitt Mission, and the Hoover-Nansen Proposal. The concluding question that frames the argument of this research will answer what happened because Wilson intervened on Russian soil and how it affected the Communist world revolution. What positive results, if any, can be discovered? (Author abstract)Rinehart, R.A. (2017) Woodrow Wilson’s diplomatic agenda and strategic military interventions: how they affected the Russian Civil War 1918-1920. Retrieved from http://academicarchive.snhu.eduMaster ArtsHistoryCollege of Online and Continuing Educatio

Cardiac Dysfunction, Congestion and Loop Diuretics: their Relationship to Prognosis in Heart Failure

Background: Diuretics are the mainstay of treatment for congestion but concerns exist that they adversely affect prognosis. We explored whether the relationship between loop diuretic use and outcome is explained by the underlying severity of congestion amongst patients referred with suspected heart failure. Method and Results: Of 1190 patients, 712 had a left ventricular ejection fraction (LVEF) ≤50 %, 267 had LVEF >50 % with raised plasma NTproBNP (>400 ng/L) and 211 had LVEF >50 % with NTproBNP ≤400 ng/L; respectively, 72 %, 68 % and 37 % of these groups were treated with loop diuretics including 28 %, 29 % and 10 % in doses ≥80 mg furosemide equivalent/day. Compared to patients with cardiac dysfunction (either LVEF ≤50 % or NT-proBNP >400 ng/L) but not taking a loop diuretic, those taking a loop diuretic were older and had more clinical evidence of congestion, renal dysfunction, anaemia and hyponatraemia. During a median follow-up of 934 (IQR: 513–1425) days, 450 patients were hospitalized for HF or died. Patients prescribed loop diuretics had a worse outcome. However, in multi-variable models, clinical, echocardiographic (inferior vena cava diameter), and biochemical (NTproBNP) measures of congestion were strongly associated with an adverse outcome but not the use, or dose, of loop diuretics. Conclusions: Prescription of loop diuretics identifies patients with more advanced features of heart failure and congestion, which may account for their worse prognosis. Further research is needed to clarify the relationship between loop diuretic agents and outcome; imaging and biochemical measures of congestion might be better guides to diuretic dose than symptoms or clinical signs