Incorporation of in silico biodegradability screening in early drug development—a feasible approach?

Introduction  

The concentration of a pharmaceutical found in the environment is determined by the amount used by the patient, the excretion and metabolism pattern, and eventually by its persistence. Biological degradation or persistence of a pharmaceutical is experimentally tested rather late in the development of a pharmaceutical, often shortly before submission of the dossier to regulatory authorities.     

Positive vs. false detection: A comparison of analytical methods and performance for analysis of cyclic volatile methylsiloxanes (cVMS) in environmental samples from remote regions

Contamination and analytical variation can significantly hinder trace analysis of cyclic methyl volatile siloxanes (cVMS); potentially resulting in the report of false positives at concentrations approaching detection limits. To assess detection and variation associated with trace cVMS analysis in environmental matrices, a co-operative laboratory comparison for the analysis of octametylcyclotetrasiloxane (D4), decamethylcylcopentasiloxane (D5), and dodecametylcyclohexasiloxane (D6) in sediment and biota from the Svalbard Archipelago was conducted. Two definitions of detection limits were evaluated in this study; method detection limits (MDL, matrix defined) and limits of detection (LOD, solvent defined). D5 was the only cVMS detected above both LOD (0.08–0.81 ng g⁻¹ ww) and MDL (0.47–2.36 ng g⁻¹ ww) within sediment by all laboratories where concentrations ranged from 0.55 to 3.91 ng g⁻¹ ww. The percentage of positive detects for D5 decreased by 80% when MDL was defined as the detection limit. D5 was also detected at the highest frequency among all laboratories in fish liver with concentrations ranging from 0.72 to 345 ng g⁻¹ ww. Similar to sediment, percentage of positive detects for D5 decreased by 60% across all laboratories for fish livers when using MDL (0.68–3.49 ng g⁻¹ ww). Similar observations were seen with both D4 and D6, indicating that sample matrix significantly contributes to analytical response variation. Despite differences in analytical methods used between laboratories, good agreement was obtained when using MDL to define detection limits. This study shows the importance of incorporating variation introduced by sample matrices into detection limit calculations to insure data accuracy of cVMS at low concentrations.     

Concentrations and specific loads of UV filters in sewage sludge originating from a monitoring network in Switzerland

Many substances related to human activities end up in wastewater and accumulate in sewage sludge. The present study focuses on the analysis of widely used UV filters 3-(4-methylbenzylidene) camphor (4-MBC), octyl-methoxycinnamate (OMC), octocrylene (OC) and octyl-triazone (OT) in sewage sludge originating from a monitoring network in Switzerland. Mean concentrations in stabilised sludge from 14 wastewater treatment plants were 1780, 110, 4840 and 5510 microg/kg dry matter for 4-MBC, OMC, OC and OT, respectively. Specific loads in sewage sludge show that UV filters originate mainly from private households, but surface runoff and industries may be considered as additional sources. This indicates that besides use for sunscreens and cosmetics UV filters might occur in plastics and other materials and be released to the environment by volatilization or leaching. Differences between the modeled per capita loads of UV filters in sewage sludge and the observed specific loads in sewage sludge are probably due to erroneous figures of production volumes, degradation and sorption during wastewater treatment as well as degradation processes during transport in the sewer or sludge treatment. Thus, further research is needed to elucidate the fate of UV filters after application and release into the environment. Other compounds used as UV filters should be included in future studies.     

What if Dutch investors started worrying about flood risk? Implications for disaster risk reduction

Regional Environmental Change - Increasingly, roles and responsibilities of the public sector in flood risk management are receiving attention in research and policy. Part of the debate suggests...     

A methodological framework to operationalize climate risk management: managing sovereign climate-related extreme event risk in Austria

Despite considerable uncertainties regarding the exact contribution of anthropogenic climate change to disaster risk, rising losses from extreme events have highlighted the need to comprehensively address climate-related risk. This requires linking climate adaptation to disaster risk management (DRM), leading to what has been broadly referred to as climate risk management (CRM). While this concept has received attention in debate, important gaps remain in terms of operationalizing it with applicable methods and tools for specific risks and decision-contexts. By developing and applying a methodological approach to CRM in the decision context of sovereign risk (flooding) in Austria we test the usefulness of CRM, and based on these insights, inform applications in other decision contexts. Our methodological approach builds on multiple lines of evidence and methods. These comprise of a broad stakeholder engagement process, empirical analysis of public budgets, and risk-focused economic modelling. We find that a CRM framework is able to inform instrumental as well as reflexive and participatory debate in practice. Due to the complex interaction of social–ecological systems with climate risks, and taking into account the likelihood of future contingent climate-related fiscal liabilities increasing substantially as a result of socioeconomic developments and climate change, we identify the need for advanced learning processes and iterative updates of CRM management plans. We suggest that strategies comprising a portfolio of policy measures to reduce and manage climate-related risks are particularly effective if they tailor individual instruments to the specific requirements of different risk layers.     

Rückstände von Bis-(Dichlorpropyl)ethern in Fischen aus der Elbe

For the first time it is reported on the residues of chlorinated bis-(dichloropropyl) ethers in fish from the Elbe-river, and their octanol/water partition coefficients.