| 1. |
- Christe, Karl O., et al.
(författare)
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Synthesis and Characterization of Fluorodinitroamine, FN(NO2)2.
- 2014
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Ingår i: Angewandte Chemie - International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 54, s. 1316-1320
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Tidskriftsartikel (refereegranskat)abstract
- NF3 and N(NO2)3 are known compds., whereas the mixed fluoronitroamines, FN(NO2)2 and F2NNO2, have been unknown thus far. One of these, FN(NO2)2, has now been prepd. and characterized by multinuclear NMR and Raman spectroscopy. FN(NO2)2 is the first known example of an inorg. fluoronitroamine. It is a thermally unstable, highly energetic material formed by the fluorination of the dinitramide anion using NF4+ salts as the preferred fluorinating agent. [on SciFinder(R)]
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| 2. |
- Heindel, Jerrold J., et al.
(författare)
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Parma consensus statement on metabolic disruptors
- 2015
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Ingår i: Environmental Health. - : BioMed Central (BMC). - 1476-069X. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- A multidisciplinary group of experts gathered in Parma Italy for a workshop hosted by the University of Parma, May 16-18, 2014 to address concerns about the potential relationship between environmental metabolic disrupting chemicals, obesity and related metabolic disorders. The objectives of the workshop were to: 1. Review findings related to the role of environmental chemicals, referred to as "metabolic disruptors", in obesity and metabolic syndrome with special attention to recent discoveries from animal model and epidemiology studies; 2. Identify conclusions that could be drawn with confidence from existing animal and human data; 3. Develop predictions based on current data; and 4. Identify critical knowledge gaps and areas of uncertainty. The consensus statements are intended to aid in expanding understanding of the role of metabolic disruptors in the obesity and metabolic disease epidemics, to move the field forward by assessing the current state of the science and to identify research needs on the role of environmental chemical exposures in these diseases. We propose broadening the definition of obesogens to that of metabolic disruptors, to encompass chemicals that play a role in altered susceptibility to obesity, diabetes and related metabolic disorders including metabolic syndrome.
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| 3. |
- Saal, Helmut, et al.
(författare)
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Determination of initial bow imperfections e(0) for second-order analysis of aluminum structures according to EN 1999-1-1
- 2016
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Ingår i: Stahlbau. - : ERNST & SOHN. - 0038-9145 .- 1437-1049. ; 85:6, s. 409-U120
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Tidskriftsartikel (refereegranskat)abstract
- The initial bow imperfection e(0) is required if structures are designed with the internal forces and moments from second-order analysis. The National Annex DIN EN 1999-1-1/NA/A1 as a NDP to 5.3.2(3) of DIN EN 1999-1-1 describes how e(0) may be calculated. Based on this, formulae are derived for calculating the relative initial bow imperfections e(0)/L for six very different types of cross sections which cover a very wide range. Linear as well as nonlinear M-N-interaction relations are used depending on the type of cross section. These formulae describe e(0)/L as product of functions of which the first depends on the cross section, the second on the proof strength f(o) and the third on relative slenderness, buckling class and interaction relation. The numerical evaluation of these formulae gives conservative limit values for e(0)/L. However, due to the wide range of the parameters these values will in general be that far on the safe side that the application of the formula with the relevant parameters is recommended. For members where fo due to the HAZ is variable over the cross section a linear and alternatively a nonlinear interaction relation may be used as safe approximation. This is demonstrated with a thin-walled circular tube.
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| 4. |
- Saal, Thomas, et al.
(författare)
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Protonation of Nitramines: Where does the Proton go
- 2017
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Ingår i: Angewandte Chemie. - : Wiley. - 1521-3773 .- 1433-7851. ; 56:32, s. 9587-9591
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Tidskriftsartikel (refereegranskat)abstract
- The reactions of nitramine, N-methyl nitramine and N,N-dimethyl nitramine with anhydrous HF and the superacids HF/MF5 (M = As, Sb) were investigated at temperatures below -40 °C. In solution, exclusive O-protonation was observed by multinuclear NMR spectroscopy. Whereas no solid product could be isolated from the neat HF solutions even at -78 °C, in the HF/MF5 systems, protonated nitramine MF6- salts were isolated for the first time as moisture-sensitive solids that decompose at temperatures above -40 °C. In the solid state, depending on the counter-ion, O-protonated or N-protonated cations can be formed, in accord with theoretical calculations which show that the energy differences between O-protonation and N-protonation are very small. The [H2N-NO2H][AsF6], [H3N-NO2][SbF6], [MeHNNO2H][SbF6], and [Me2NNO2H][SbF6] salts were characterized by their X-ray crystal structures.
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| 5. |
- Schug, Thaddeus T., et al.
(författare)
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Designing Endocrine Disruption Out of the Next Generation of Chemicals
- 2013
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Ingår i: Green Chemistry. - : Royal Society of Chemistry. - 1463-9262 .- 1463-9270. ; 15:1, s. 181-198
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Tidskriftsartikel (refereegranskat)abstract
- A central goal of green chemistry is to avoid hazard in the design of new chemicals. This objective is best achieved when information about a chemical's potential hazardous effects is obtained as early in the design process as feasible. Endocrine disruption is a type of hazard that to date has been inadequately addressed by both industrial and regulatory science. To aid chemists in avoiding this hazard, we propose an endocrine disruption testing protocol for use by chemists in the design of new chemicals. The Tiered Protocol for Endocrine Disruption (TiPED) has been created under the oversight of a scientific advisory committee composed of leading representatives from both green chemistry and the environmental health sciences. TiPED is conceived as a tool for new chemical design, thus it starts with a chemist theoretically at "the drawing board." It consists of five testing tiers ranging from broad in silico evaluation up through specific cell- and whole organism-based assays. To be effective at detecting endocrine disruption, a testing protocol must be able to measure potential hormone-like or hormone-inhibiting effects of chemicals, as well as the many possible interactions and signaling sequellae such chemicals may have with cell-based receptors. Accordingly, we have designed this protocol to broadly interrogate the endocrine system. The proposed protocol will not detect all possible mechanisms of endocrine disruption, because scientific understanding of these phenomena is advancing rapidly. To ensure that the protocol remains current, we have established a plan for incorporating new assays into the protocol as the science advances. In this paper we present the principles that should guide the science of testing new chemicals for endocrine disruption, as well as principles by which to evaluate individual assays for applicability, and laboratories for reliability. In a 'proof-of-principle' test, we ran 6 endocrine disrupting chemicals (EDCs) that act via different endocrinological mechanisms through the protocol using published literature. Each was identified as endocrine active by one or more tiers. We believe that this voluntary testing protocol will be a dynamic tool to facilitate efficient and early identification of potentially problematic chemicals, while ultimately reducing the risks to public health.
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| 6. |
- Trasande, Leonardo, et al.
(författare)
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Peer-reviewed and unbiased research, rather than 'sound science', should be used to evaluate endocrine-disrupting chemicals
- 2016
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Ingår i: Journal of Epidemiology and Community Health. - : BMJ Publishing Group Ltd. - 0143-005X .- 1470-2738. ; 70:11, s. 1051-1056
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Tidskriftsartikel (refereegranskat)abstract
- Evidence increasingly confirms that synthetic chemicals disrupt the endocrine system and contribute to disease and disability across the lifespan. Despite a United Nations Environment Programme/WHO report affirmed by over 100 countries at the Fourth International Conference on Chemicals Management, 'manufactured doubt' continues to be cast as a cloud over rigorous, peer-reviewed and independently funded scientific data. This study describes the sources of doubt and their social costs, and suggested courses of action by policymakers to prevent disease and disability. The problem is largely based on the available data, which are all too limited. Rigorous testing programmes should not simply focus on oestrogen, androgen and thyroid. Tests should have proper statistical power. 'Good laboratory practice' (GLP) hardly represents a proper or even gold standard for laboratory studies of endocrine disruption. Studies should be evaluated with regard to the contamination of negative controls, responsiveness to positive controls and dissection techniques. Flaws in many GLP studies have been identified, yet regulatory agencies rely on these flawed studies. Peer-reviewed and unbiased research, rather than 'sound science', should be used to evaluate endocrine-disrupting chemicals.
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| 7. |
- Vandenberg, Laura N., et al.
(författare)
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Regulatory decisions on endocrine disrupting chemicals should be based on the principles of endocrinology
- 2013
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Ingår i: Reproductive Toxicology. - : Elsevier. - 0890-6238 .- 1873-1708. ; 38, s. 1-15
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Forskningsöversikt (refereegranskat)abstract
- For years, scientists from various disciplines have studied the effects of endocrine disrupting chemicals (EDCs) on the health and wellbeing of humans and wildlife. Some studies have specifically focused on the effects of low doses, i.e. those in the range that are thought to be safe for humans and/or animals. Others have focused on the existence of non-monotonic dose-response curves. These concepts challenge the way that chemical risk assessment is performed for EDCs. Continued discussions have clarified exactly what controversies and challenges remain. We address several of these issues, including why the study and regulation of EDCs should incorporate endocrine principles; what level of consensus there is for low dose effects; challenges to our understanding of non-monotonicity; and whether EDCs have been demonstrated to produce adverse effects. This discussion should result in a better understanding of these issues, and allow for additional dialog on their impact on risk assessment.
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| 8. |
- Zardavas, Dimitrios, et al.
(författare)
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Tumor PIK3CA Genotype and Prognosis in Early-Stage Breast Cancer: A Pooled Analysis of Individual Patient Data
- 2018
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Ingår i: Journal of Clinical Oncology. - : AMER SOC CLINICAL ONCOLOGY. - 0732-183X .- 1527-7755. ; 36:10, s. 981-
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Tidskriftsartikel (refereegranskat)abstract
- PurposePhosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations are frequently observed in primary breast cancer. We evaluated their prognostic relevance by performing a pooled analysis of individual patient data.Patients and MethodsAssociations between PIK3CA status and clinicopathologic characteristics were tested by applying Cox regression models adjusted for age, tumor size, nodes, grade, estrogen receptor (ER) status, human epidermal growth factor receptor 2 (HER2) status, treatment, and study. Invasive disease-free survival (IDFS) was the primary end point; distant disease-free survival (DDFS) and overall survival (OS) were also assessed, overall and by breast cancer subtypes.ResultsData from 10,319 patients from 19 studies were included (median OS follow-up, 6.9 years); 1,787 patients (17%) received chemotherapy, 4,036 (39%) received endocrine monotherapy, 3,583 (35%) received both, and 913 (9%) received none or their treatment was unknown. PIK3CA mutations occurred in 32% of patients, with significant associations with ER positivity, increasing age, lower grade, and smaller size (all P amp;lt; .001). Prevalence of PIK3CA mutations was 18%, 22%, and 37% in the ER-negative/HER2-negative, HER2-positive, and ER-positive/HER2-negative subtypes, respectively. In univariable analysis, PIK3CA mutations were associated with better IDFS (HR, 0.77; 95% CI, 0.71 to 0.84; P amp;lt; .001), with evidence for a stronger effect in the first years of follow-up (0 to 5 years: HR, 0.73; 95% CI, 0.66 to 0.81; P amp;lt; .001; 5 to 10 years: HR, 0.82; 95% CI, 0.68 to 0.99; P = .037); amp;gt; 10 years: (HR, 1.15; 95% CI, 0.84 to 1.58; P = .38; P heterogeneity = .02). In multivariable analysis, PIK3CA genotype remained significant for improved IDFS (P = .043), but not for the DDFS and OS end points.ConclusionIn this large pooled analysis, PIK3CA mutations were significantly associated with a better IDFS, DDFS, and OS, but had a lesser prognostic effect after adjustment for other prognostic factors. (C) 2018 by American Society of Clinical Oncology
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| 9. |
- Zoeller, R. Thomas, 1952-, et al.
(författare)
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European Medicines Agency Conflicts With the European Food Safety Authority (EFSA) on Bisphenol A Regulation
- 2023
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Ingår i: Journal of the Endocrine Society. - : Oxford University Press. - 2472-1972. ; 7:9
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Tidskriftsartikel (refereegranskat)abstract
- The European Food Safety Authority (EFSA) has revised their estimate of the toxicity of bisphenol A (BPA) and, as a result, have recommended reducing the tolerable daily intake (TDI) by 20 000-fold. This would essentially ban the use of BPA in food packaging such as can liners, plastic food containers, and in consumer products. To come to this conclusion, EFSA used a systematic approach according to a pre-established protocol and included all guideline and nonguideline studies in their analysis. They found that Th-17 immune cells increased with very low exposure to BPA and used this endpoint to revise the TDI to be human health protective. A number of regulatory agencies including the European Medicines Agency (EMA) have written formal disagreements with several elements of EFSA's proposal. The European Commission will now decide whether to accept EFSA's recommendation over the objections of EMA. If the Commission accepts EFSA's recommendation, it will be a landmark action using knowledge acquired through independent scientific studies focused on biomarkers of chronic disease to protect human health. The goal of this Perspective is to clearly articulate the monumental nature of this debate and decision and to explain what is at stake. Our perspective is that the weight of evidence clearly supports EFSA's proposal to reduce the TDI by 20 000-fold.
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