A Mechanistic Modeling Framework for Predicting Metabolic Interactions in Complex Mixtures

Background: Computational modeling of the absorption, distribution, metabolism, and excretion of chemicals is now theoretically able to describe metabolic interactions in realistic mixtures of tens to hundreds of substances. That framework awaits validation

Report from the EPAA workshop: In vitro ADME in safety testing used by EPAA industry sectors

AbstractThere are now numerous in vitro and in silico ADME alternatives to in vivo assays but how do different industries incorporate them into their decision tree approaches for risk assessment, bearing in mind that the chemicals tested are intended for widely varying purposes? The extent of the use of animal tests is mainly driven by regulations or by the lack of a suitable in vitro model. Therefore, what considerations are needed for alternative models and how can they be improved so that they can be used as part of the risk assessment process? To address these issues, the European Partnership for Alternative Approaches to Animal Testing (EPAA) working group on prioritisation, promotion and implementation of the 3Rs research held a workshop in November, 2008 in Duesseldorf, Germany. Participants included different industry sectors such as pharmaceuticals, cosmetics, industrial- and agro-chemicals. This report describes the outcome of the discussions and recommendations (a) to reduce the number of animals used for determining the ADME properties of chemicals and (b) for considerations and actions regarding in vitro and in silico assays. These included: standardisation and promotion of in vitro assays so that they may become accepted by regulators; increased availability of industry in vivo kinetic data for a central database to increase the power of in silico predictions; expansion of the applicability domains of in vitro and in silico tools (which are not necessarily more applicable or even exclusive to one particular sector) and continued collaborations between regulators, academia and industry. A recommended immediate course of action was to establish an expert panel of users, developers and regulators to define the testing scope of models for different chemical classes. It was agreed by all participants that improvement and harmonization of alternative approaches is needed for all sectors and this will most effectively be achieved by stakeholders from different sectors sharing data

Agronomic Evaluation of Bread Wheat Varieties from Participatory Breeding: A Combination of Performance and Robustness

Participatory plant breeding (PPB) is based on the decentralization of selection in farmers’ fields and their involvement in decision-making at all steps of the breeding scheme. Despite the evidence of its benefits to develop population varieties adapted to diversified and local practices and conditions, such as organic farming, PPB is still not widely used. There is a need to share more broadly how the different programs have overcome scientific, practical, and organizational issues and produced a large number of positive outcomes. Here, we report on a PPB program that started on bread wheat in France in 2006 and has achieved a range of outcomes, from the emergence of new organization among actors, to specific experimental designs and statistical methods developed, and to populations varieties developed and cultivated by farmers. We present the results of a two-year agronomic evaluation of the first population varieties developed within this PPB program compared to two commercial varieties currently grown in organic agriculture. We found that several PPB varieties were of great agronomic interest, combining relatively good performance even under the most favorable conditions of organic agriculture and good robustness, i.e., the ability to maintain productivity under more constraining conditions. The PPB varieties also tended to show a good temporal dynamic stability and appeared promising for the farmers involved

Phylogenetic analysis of putative COMT proteins.

<p>Phylogeny tree (phylogram) made with OMT proteins from Brachypodium (BdCOMT), rice (OsOMT), maize (ZmOMT) and Arabidopsis (AtOMT). The proteins known to be involved in lignification in ryegrass (LpCOMT), sorghum (SbCOMT), switchgrass (PvCOMT), fescue (FaCOMT) and poplar (PtCOMT) are included in the analysis and shown in red in the phylogram as well as Arabidopsis (AtOMT1) and Maize (ZmCOMT1) proteins. Brachypodium proteins (BdCOMT) are shown in green. Protein sequences are available in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065503#pone.0065503.s001" target="_blank">Information S1</a>. Bootstrap values indicating the level of support for the displayed representation after re-sampling are shown on each node.</p