Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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    Enabling reusability of plant phenomic datasets with MIAPPE 1.1
    Papoutsoglou, Evangelia A. ; Faria, Daniel ; Arend, Daniel ; Arnaud, Elizabeth ; Athanasiadis, Ioannis N. ; Chaves, Inês ; Coppens, Frederik ; Cornut, Guillaume ; Costa, Bruno V. ; Ćwiek-Kupczyńska, Hanna ; Droesbeke, Bert ; Finkers, Richard ; Gruden, Kristina ; Junker, Astrid ; King, Graham J. ; Krajewski, Paweł ; Lange, Matthias ; Laporte, Marie Angélique ; Michotey, Célia ; Oppermann, Markus ; Ostler, Richard ; Poorter, Hendrik ; Ramı́rez-Gonzalez, Ricardo ; Ramšak, Živa ; Reif, Jochen C. ; Rocca-Serra, Philippe ; Sansone, Susanna Assunta ; Scholz, Uwe ; Tardieu, François ; Uauy, Cristobal ; Usadel, Björn ; Visser, Richard G.F. ; Weise, Stephan ; Kersey, Paul J. ; Miguel, Célia M. ; Adam-Blondon, Anne Françoise ; Pommier, Cyril - \ 2020
    New Phytologist 227 (2020)1. - ISSN 0028-646X - p. 260 - 273.
    findability - interoperability - metadata - phenomics - plant phenotyping - reusability - standards

    Enabling data reuse and knowledge discovery is increasingly critical in modern science, and requires an effort towards standardising data publication practices. This is particularly challenging in the plant phenotyping domain, due to its complexity and heterogeneity. We have produced the MIAPPE 1.1 release, which enhances the existing MIAPPE standard in coverage, to support perennial plants, in structure, through an explicit data model, and in clarity, through definitions and examples. We evaluated MIAPPE 1.1 by using it to express several heterogeneous phenotyping experiments in a range of different formats, to demonstrate its applicability and the interoperability between the various implementations. Furthermore, the extended coverage is demonstrated by the fact that one of the datasets could not have been described under MIAPPE 1.0. MIAPPE 1.1 marks a major step towards enabling plant phenotyping data reusability, thanks to its extended coverage, and especially the formalisation of its data model, which facilitates its implementation in different formats. Community feedback has been critical to this development, and will be a key part of ensuring adoption of the standard.

    Learning about learning in sustainability transitions
    Mierlo, Barbara van; Halbe, Johannes ; Beers, Pieter J. ; Scholz, Geeske ; Vinke-de Kruijf, Joanne - \ 2020
    Environmental Innovation and Societal Transitions 34 (2020). - ISSN 2210-4224 - p. 251 - 254.
    BrAPI-an application programming interface for plant breeding applications
    Selby, Peter ; Abbeloos, Rafael ; Backlund, Jan Erik ; Basterrechea Salido, Martin ; Bauchet, Guillaume ; Benites-Alfaro, Omar E. ; Birkett, Clay ; Calaminos, Viana C. ; Carceller, Pierre ; Cornut, Guillaume ; Vasques Costa, Bruno ; Edwards, Jeremy D. ; Finkers, Richard ; Yanxin Gao, Star ; Ghaffar, Mehmood ; Glaser, Philip ; Guignon, Valentin ; Hok, Puthick ; Kilian, Andrzej ; König, Patrick ; Lagare, Jack Elendil B. ; Lange, Matthias ; Laporte, Marie Angélique ; Larmande, Pierre ; LeBauer, David S. ; Lyon, David A. ; Marshall, David S. ; Matthews, Dave ; Milne, Iain ; Mistry, Naymesh ; Morales, Nicolas ; Mueller, Lukas A. ; Neveu, Pascal ; Papoutsoglou, Evangelia ; Pearce, Brian ; Perez-Masias, Ivan ; Pommier, Cyril ; Ramírez-González, Ricardo H. ; Rathore, Abhishek ; Raquel, Angel Manica ; Raubach, Sebastian ; Rife, Trevor ; Robbins, Kelly ; Rouard, Mathieu ; Sarma, Chaitanya ; Scholz, Uwe ; Sempéré, Guilhem ; Shaw, Paul D. ; Simon, Reinhard ; Verouden, Maikel - \ 2019
    Bioinformatics 35 (2019)20. - ISSN 1367-4803 - p. 4147 - 4155.

    MOTIVATION: Modern genomic breeding methods rely heavily on very large amounts of phenotyping and genotyping data, presenting new challenges in effective data management and integration. Recently, the size and complexity of datasets have increased significantly, with the result that data are often stored on multiple systems. As analyses of interest increasingly require aggregation of datasets from diverse sources, data exchange between disparate systems becomes a challenge. RESULTS: To facilitate interoperability among breeding applications, we present the public plant Breeding Application Programming Interface (BrAPI). BrAPI is a standardized web service API specification. The development of BrAPI is a collaborative, community-based initiative involving a growing global community of over a hundred participants representing several dozen institutions and companies. Development of such a standard is recognized as critical to a number of important large breeding system initiatives as a foundational technology. The focus of the first version of the API is on providing services for connecting systems and retrieving basic breeding data including germplasm, study, observation, and marker data. A number of BrAPI-enabled applications, termed BrAPPs, have been written, that take advantage of the emerging support of BrAPI by many databases. AVAILABILITY AND IMPLEMENTATION: More information on BrAPI, including links to the specification, test suites, BrAPPs, and sample implementations is available at The BrAPI specification and the developer tools are provided as free and open source.

    Biogeography of the fish pathogen Aeromonas salmonicida inferred by vapA genotyping
    Gulla, Snorre ; Bayliss, Sion ; Björnsdóttir, Bryndís ; Dalsgaard, Inger ; Haenen, Olga ; Jansson, Eva ; McCarthy, Una ; Scholz, Felix ; Vercauteren, Maaike ; Verner-Jeffreys, David ; Welch, Tim ; Wiklund, Tom ; Colquhoun, Duncan J. - \ 2019
    FEMS Microbiology Letters 366 (2019)7. - ISSN 0378-1097
    Aeromonas salmonicida - aquaculture - bacterial fish pathogen - genotyping - host specificity - vapA/A-layer

    A recently described typing system based on sequence variation in the virulence array protein (vapA) gene, encoding the A-layer surface protein array, allows unambiguous subtyping of Aeromonas salmonicida. In the present study, we compile A-layer typing results from a total of 675 A. salmonicida isolates, recovered over a 59-year period from 50 different fish species in 26 countries. Nine novel A-layer types (15-23) are identified, several of which display a strong predilection towards certain fish hosts, including e.g. Cyprinidae and Pleuronectidae species. Moreover, we find indications that anthropogenic transport of live fish may have aided the near global dissemination of two cyprinid-associated A-layer types. Comparison of whole genome phylogeny and A-layer typing for a subset of strains further resulted in compatible tree topologies, indicating the utility of vapA as a phylogenetic as well as an epizootiological marker in A. salmonicida. A Microreact project ( has been created, allowing public access to the vapA analyses and relevant metadata. In sum, the results generated provide valuable insights into the global population structure of A. salmonicida, particularly in relation to its piscine host spectrum and the geographic distribution of these hosts.

    Corrigendum: Towards recommendations for metadata and data handling in plant phenotyping
    Krajewski, Paweł ; Chen, Dijun ; Ćwiek, Hanna ; Dijk, Aalt D.J. Van; Fiorani, Fabio ; Kersey, Paul ; Klukas, Christian ; Lange, Matthias ; Markiewicz, Augustyn ; Nap, Jan Peter ; Oeveren, Jan Van; Pommier, Cyril ; Scholz, Uwe ; Schriek, Marco Van; Usadel, Björn ; Weise, Stephan - \ 2018
    Journal of Experimental Botany 69 (2018)7. - ISSN 0022-0957 - p. 1819 - 1819.
    Exposure assessment of process-related contaminants in food by biomarker monitoring
    Rietjens, Ivonne M.C.M. ; Dussort, P. ; Günther, Helmut ; Hanlon, Paul ; Honda, Hiroshi ; Mally, Angela ; O’Hagan, Sue ; Scholz, Gabriele ; Seidel, Albrecht ; Swenberg, James ; Teeguarden, Justin ; Eisenbrand, Gerhard - \ 2018
    Archives of Toxicology 92 (2018)1. - ISSN 0340-5761 - p. 15 - 40.
    Biomarkers - Dietary process-related contaminants - External exposure assessment - Physiologically based kinetic models - Risk assessment
    Exposure assessment is a fundamental part of the risk assessment paradigm, but can often present a number of challenges and uncertainties. This is especially the case for process contaminants formed during the processing, e.g. heating of food, since they are in part highly reactive and/or volatile, thus making exposure assessment by analysing contents in food unreliable. New approaches are therefore required to accurately assess consumer exposure and thus better inform the risk assessment. Such novel approaches may include the use of biomarkers, physiologically based kinetic (PBK) modelling-facilitated reverse dosimetry, and/or duplicate diet studies. This review focuses on the state of the art with respect to the use of biomarkers of exposure for the process contaminants acrylamide, 3-MCPD esters, glycidyl esters, furan and acrolein. From the overview presented, it becomes clear that the field of assessing human exposure to process-related contaminants in food by biomarker monitoring is promising and strongly developing. The current state of the art as well as the existing data gaps and challenges for the future were defined. They include (1) using PBK modelling and duplicate diet studies to establish, preferably in humans, correlations between external exposure and biomarkers; (2) elucidation of the possible endogenous formation of the process-related contaminants and the resulting biomarker levels; (3) the influence of inter-individual variations and how to include that in the biomarker-based exposure predictions; (4) the correction for confounding factors; (5) the value of the different biomarkers in relation to exposure scenario’s and risk assessment, and (6) the possibilities of novel methodologies. In spite of these challenges it can be concluded that biomarker-based exposure assessment provides a unique opportunity to more accurately assess consumer exposure to process-related contaminants in food and thus to better inform risk assessment.
    The European 2015 drought from a climatological perspective
    Ionita, Monica ; Tallaksen, Lena M. ; Kingston, Daniel G. ; Stagge, James H. ; Laaha, Gregor ; Lanen, Henny A.J. Van; Scholz, Patrick ; Chelcea, Silvia M. ; Haslinger, Klaus - \ 2017
    Hydrology and Earth System Sciences 21 (2017)3. - ISSN 1027-5606 - p. 1397 - 1419.
    The summer drought of 2015 affected a large portion of continental Europe and was one of the most severe droughts in the region since summer 2003. The summer of 2015 was characterized by exceptionally high temperatures in many parts of central and eastern Europe, with daily maximum temperatures 2 °C higher than the seasonal mean (1971-2000) over most of western Europe, and more than 3 °C higher in the east. It was the hottest and climatologically driest summer over the 1950-2015 study period for an area stretching from the eastern Czech Republic to Ukraine. For Europe, as a whole, it is among the six hottest and driest summers since 1950. High evapotranspiration rates combined with a lack of precipitation affected soil moisture and vegetation and led to record low river flows in several major rivers, even beyond the drought-hit region. The 2015 drought developed rather rapidly over the Iberian Peninsula, France, southern Benelux and central Germany in May and reached peak intensity and spatial extent by August, affecting especially the eastern part of Europe. Over the summer period, there were four heat wave episodes, all associated with persistent blocking events. Upper-level atmospheric circulation over Europe was characterized by positive 500 hPa geopotential height anomalies flanked by a large negative anomaly to the north and west (i.e., over the central North Atlantic Ocean extending to northern Fennoscandia) and another center of positive geopotential height anomalies over Greenland and northern Canada. Simultaneously, the summer sea surface temperatures (SSTs) were characterized by large negative anomalies in the central North Atlantic Ocean and large positive anomalies in the Mediterranean basin. Composite analysis shows that the western Mediterranean SST is strongly related to the occurrence of dry and hot summers over the last 66 years (especially over the eastern part of Europe). The lagged relationship between the Mediterranean SST and summer drought conditions established in this study can provide valuable skill for the prediction of drought conditions over Europe on interannual to decadal timescales.
    Evaluation of Interindividual Human Variation in Bioactivation and DNA Adduct Formation of Estragole in Liver Predicted by Physiologically Based Kinetic/Dynamic and Monte Carlo Modeling
    Punt, Ans ; Paini, Alicia ; Spenkelink, Bert ; Scholz, Gabriele ; Schilter, Benoit ; Bladeren, Peter J. Van; Rietjens, Ivonne M.C.M. - \ 2016
    Chemical Research in Toxicology 29 (2016)4. - ISSN 0893-228X - p. 659 - 668.

    Estragole is a known hepatocarcinogen in rodents at high doses following metabolic conversion to the DNA-reactive metabolite 1′-sulfooxyestragole. The aim of the present study was to model possible levels of DNA adduct formation in (individual) humans upon exposure to estragole. This was done by extending a previously defined PBK model for estragole in humans to include (i) new data on interindividual variation in the kinetics for the major PBK model parameters influencing the formation of 1′-sulfooxyestragole, (ii) an equation describing the relationship between 1′-sulfooxyestragole and DNA adduct formation, (iii) Monte Carlo modeling to simulate interindividual human variation in DNA adduct formation in the population, and (iv) a comparison of the predictions made to human data on DNA adduct formation for the related alkenylbenzene methyleugenol. Adequate model predictions could be made, with the predicted DNA adduct levels at the estimated daily intake of estragole of 0.01 mg/kg bw ranging between 1.6 and 8.8 adducts in 108 nucleotides (nts) (50th and 99th percentiles, respectively). This is somewhat lower than values reported in the literature for the related alkenylbenzene methyleugenol in surgical human liver samples. The predicted levels seem to be below DNA adduct levels that are linked with tumor formation by alkenylbenzenes in rodents, which were estimated to amount to 188-500 adducts per 108 nts at the BMD10 values of estragole and methyleugenol. Although this does not seem to point to a significant health concern for human dietary exposure, drawing firm conclusions may have to await further validation of the model's predictions.

    Towards a common nutrient use efficiency assessment method for livestock supply chains: : a case study of mixed dairy supply chains in western europe
    Uwizeye, U.A. ; Gerber, P.J. ; Schulte, R.P.O. ; Boer, I.J.M. de - \ 2015
    The comprehensive assessment of efficiency of nitrogen (N) and phosphorus (P) use in livestock supply chains is a key step towards sustainable nutrient management [1]. Previously, we identified supply chain level nutrient use efficiency (life-cycle NUE), as a pertinent indicator to support monitoring of practice changes and benchmarking of livestock supply chains [2]. The quantification of life-cycle NUE [3] requires the computation of NUE at each stage of supply chain, including crop/pasture production, animal production and processing. A ‘perfect’ NUE assessment in crop/pasture production would require measurement of all nutrient flows, including inputs, soil stock changes (SSC), losses and removals in harvested biomass. However, no dataset could be found that includes comprehensive measurement of both SSC and losses. Therefore, existing models commonly estimate the value of these variables by modelling one of these two flows and deriving the other from mass balance. The aim of this study, part of the FAO Livestock Environmental Assessment and Performance (LEAP) partnership, was to assess the extent to which reported life-cycle NUE values depend on such methodological choices. We compared three N accounting approaches: i) a simple input-output approach where SSC is set to equal 0 [4], ii) an approach where N losses are modelled [5] and iii) an approach where SSC is modelled, based on assumptions about NUE values [6]. Additionally, for P-NUE, we explored methodological approaches to account for “sustainable fertility build-up” in P-deficient and optimum soils [7]. We illustrate both these N and P assessments for mixed dairy systems in Western Europe.

    [1] M.A. Sutton, A. Bleeker, C. Howard, M. Bekunda, B. Grizzetti, W. de Vries, et al., Our Nutrient World: the challenge to produce more food and energy with less pollution. Global Overview of Nutrient Management, Sutton, M. A.;Bleeker, A.;Howard, C. M.;Bekunda, M.;Grizzetti, B.;Vries, W. de;Grinsven, H. J. M. van;Abrol, Y. P.;Adhya, T. K.;Billen, G.;Davidson, E. A.;Datta, A.;Diaz, R.;Erisman, J. W.;Liu, X. J.;Oenema, O.;Palm, C.;Raghuram, N.;Reis, S.;Scholz, R. W.;Sims, T.;Westhoek, H.;Zhang, F. S., CEH/UNEP, Edinburgh, UK, 2013.
    [2] P. Gerber, A. Uwizeye, R. Schulte, C. Opio, I. de Boer, Nutrient use efficiency: a valuable approach to benchmark the sustainability of nutrient use in global livestock production?, SI Syst. Dyn. Sustain. 9–10 (2014) 122–130. doi:10.1016/j.cosust.2014.09.007.
    [3] S. Suh, S. Yee, Phosphorus use-efficiency of agriculture and food system in the US, Phosphorus Cycle. 84 (2011) 806–813. doi:10.1016/j.chemosphere.2011.01.051.
    [4] E. OECD, Gross Nitrogen Balances-Handbook, URL. 20 (2007) 2010.
    [5] G. Velthof, D. Oudendag, H. Witzke, W. Asman, Z. Klimont, O. Oenema, Integrated assessment of nitrogen losses from agriculture in EU-27 using MITERRA-EUROPE, J. Environ. Qual. 38 (2009) 402–417.
    [6] F.Ş. Özbek, A. Leip, Estimating the gross nitrogen budget under soil nitrogen stock changes: A case study for Turkey, Agric. Ecosyst. Environ. 205 (2015) 48–56.
    [7] G. Tóth, A. Jones, L. Montanarella, The LUCAS topsoil database and derived information on the regional variability of cropland topsoil properties in the European Union, Environ. Monit. Assess. 185 (2013) 7409–7425. doi:10.1007/s10661-013-3109-3.

    Towards recommendations for metadata and data handling in plant phenotyping
    Krajewski, P. ; Chen, D. ; Cwiek, H. ; Dijk, A.D.J. van; Fiorani, F. ; Kersey, P. ; Klukas, C. ; Lange, M. ; Markiewicz, A. ; Nap, J.P.H. ; Oeveren, J. van; Pommier, P. ; Scholz, U. ; Schriek, M. van; Usadel, B. ; Weise, S. - \ 2015
    Journal of Experimental Botany 66 (2015)18. - ISSN 0022-0957 - p. 5417 - 5427.
    Recent methodological developments in plant phenotyping, as well as the growing importance of its applications in plant science and breeding, are resulting in a fast accumulation of multidimensional data. There is great potential for expediting both discovery and application if these data are made publicly available for analysis. However, collection and storage of phenotypic observations is not yet sufficiently governed by standards that would ensure interoperability among data providers and precisely link specific phenotypes and associated genomic sequence information. This lack of standards is mainly a result of a large variability of phenotyping protocols, the multitude of phenotypic traits that are measured, and the dependence of these traits on the environment. This paper discusses the current situation of standardization in the area of phenomics, points out the problems and shortages, and presents the areas that would benefit from improvement in this field. In addition, the foundations of the work that could revise the situation are proposed, and practical solutions developed by the authors are introduced.
    Framework to determine the effectiveness of dietary exposure mitigation to chemical contaminants
    Fels, H.J. van der; Edwards, S. ; Kennedy, M. ; O'Hagan, A. ; O'Mahony, C. ; Scholz, G. ; Steinberg, P. ; Tennant, D. ; Chiodini, A. - \ 2014
    Food and Chemical Toxicology 74 (2014). - ISSN 0278-6915 - p. 360 - 371.
    chromatography-mass spectrometry - solid-phase microextraction - extraction-gas chromatography - single-laboratory validation - fusarium mycotoxin content - methyl mercury exposure - spme-gc-ms - risk-assessment - baby-food - fish consumption
    In order to ensure the food safety, risk managers may implement measures to reduce human exposure to contaminants via food consumption. The evaluation of the effect of a measure is often an overlooked step in risk analysis process. The aim of this study was to develop a systematic approach for determining the effectiveness of mitigation measures to reduce dietary exposure to chemical contaminants. Based on expert opinion, a general framework for evaluation of the effectiveness of measures to reduce human exposure to food contaminants was developed. The general outline was refined by application to three different cases: 1) methyl mercury in fish and fish products, 2) deoxynivalenol in cereal grains, and 3) furan in heated products. It was found that many uncertainties and natural variations exist, which make it difficult to assess the impact of the mitigation measure. Whenever possible, quantitative methods should be used to describe the current variation and uncertainty. Additional data should be collected to cover natural variability and reduce uncertainty. For the time being, it is always better for the risk manager to have access to all available information, including an assessment of uncertainty; however, the proposed methodology provides a conceptual framework for addressing these systematically.
    How participatory methods facilitate social learning in natural resource management: an exploration of group interaction using interdisciplinary syntheses and agent-based modeling
    Scholz, G. - \ 2014
    University of Osnabrück. Promotor(en): C. Pahl-Wostl, co-promotor(en): Art Dewulf. -
    High-resolution mapping of the barley Ryd3 locus controlling tolerance to BYDV
    Lüpken, T. ; Stein, N. ; Perovic, D. ; Habekuss, A. ; Serfling, A. ; Krämer, I. ; Hähnel, U. ; Steuernagel, B. ; Scholz, U. ; Ariyadasa, R. ; Martis, M. ; Mayer, K. ; Niks, R.E. ; Collins, N.C. ; Friedt, W. ; Ordon, F. - \ 2014
    Molecular Breeding 33 (2014)2. - ISSN 1380-3743 - p. 477 - 488.
    yellow-dwarf-virus - hordeum-vulgare l. - recessive bymovirus resistance - leaf rust resistance - comparative genomics - consensus map - winter barley - linkage map - yd2 gene - sequence
    Barley yellow dwarf disease (BYD) is transmitted by aphids and is caused by different strains of Barley yellow dwarf virus (BYDV) and Cereal yellow dwarf virus (CYDV). Economically it is one of the most important diseases of cereals worldwide. Besides chemical control of the vector, growing of tolerant/resistant cultivars is an effective way of protecting crops against BYD. The Ryd3 gene in barley (Hordeum vulgare L.) confers tolerance to BYDV-PAV and BYDV-MAV and the locus was previously mapped on the short arm of barley chromosome 6H near the centromere. We applied a strategy for high-resolution mapping and marker saturation at the Ryd3 locus by exploiting recent genomic tools available in barley. In a population of 3,210 F2 plants, 14 tightly linked markers were identified, including 10 that co-segregated with Ryd3. The centromeric region where Ryd3 is located suffers suppressed recombination or reduced recombination rate, suggesting potential problems in achieving (1) map-based cloning of Ryd3 and (2) marker selection of the resistance in breeding programmes without the introduction of undesirable traits via linkage drag.
    An Analytical framework of social learning facilitated by participatory methods
    Scholz, G. ; Dewulf, A. ; Pahl-Wostl, C. - \ 2014
    Systemic Practice and Action Research 27 (2014)6. - ISSN 1094-429X - p. 575 - 591.
    resources management - water management - mental models - environmental-management - ecological-systems - governance - transition - culture - science
    Social learning among different stakeholders is often a goal in problem solving contexts such as environmental management. Participatory methods (e.g., group model-building and role playing games) are frequently assumed to stimulate social learning. Yet understanding if and why this assumption is justified is quite limited. Difficulties arise from the complexity and context-dependence of processes influencing social learning. Furthermore, continuing discussion of the exact meaning and theoretical basis of social learning result in a limited capacity to assess and evaluate whether social learning has occurred. In this paper we introduce an analytical framework to develop an in depth understanding of essential processes underlying social learning facilitated by participatory methods. Concepts from different fields of science are discussed and integrated, including resource management, small group research and learning research. The individual and group perspectives are brought together via mental models and emergent roles. We added the direction of learning, being either convergent or divergent, to be able to explore if and when personal views on a problem converge into a shared understanding of a problem. The analysis of convergence and divergence of learning is facilitated through the use of the mental model concept. Methods for measurement of proposed indicators for social learning are also discussed. The framework developed provides a conceptual basis for the analysis of social learning facilitated by participatory methods and an operationalization for application in empirical research. Keywords Social learning – Resources management – Mental model – Role – Participatory method – Shared understanding
    In vivo validation and physiologically based biokinetic modeling of the inhibition of SULT-mediated estragole DNA adduct formation in the liver of male Sprague-Dawley rats by the basil flavonoid nevadensin
    Alhusainy, W. ; Paini, A. ; Berg, J.H.J. van den; Punt, A. ; Scholz, G. ; Schilter, B. ; Bladeren, P.J. van; Taylor, S. ; Adams, T.B. ; Rietjens, I. - \ 2013
    Molecular Nutrition & Food Research 57 (2013)11. - ISSN 1613-4125 - p. 1969 - 1978.
    naturally-occurring alkenylbenzenes - post-labeling analysis - mouse-liver - intestinal-absorption - metabolic stability - mice - safrole - 1'-hydroxyestragole - bioactivation - sulfotransferases
    ScopeThe present work investigates whether the previous observation that the basil flavonoid nevadensin is able to inhibit sulfotransferase (SULT)-mediated estragole DNA adduct formation in primary rat hepatocytes could be validated in vivo. Methods and resultsEstragole and nevadensin were co-administered orally to Sprague-Dawley rats, at a ratio reflecting their presence in basil. Moreover, previously developed physiologically based biokinetic (PBBK) models to study this inhibition in rat and in human liver were refined by including a submodel describing nevadensin kinetics. Nevadensin resulted in a significant 36% reduction in the levels of estragole DNA adducts formed in the liver of rats. The refined PBBK model predicts the formation of estragole DNA adducts in the liver of rat with less than twofold difference compared to in vivo data and suggests more potent inhibition in the liver of human compared to rat due to less efficient metabolism of nevadensin in human liver and intestine. ConclusionGiven the role of the SULT-mediated DNA adduct formation in the hepatocarcinogenicity of estragole, the results of the present study suggest that the likelihood of bioactivation and subsequent adverse effects in rodent bioassays may be lower when estragole is dosed with nevadensin compared to dosing of pure estragole.
    A European perspective on alternatives to animal testing for environmental hazard identification and risk assessment
    Scholz, S. ; Sela, E. ; Blaha, L. ; Braunbeck, T. ; Galay-Burgos, M. ; Garcia-Franco, M. ; Guinea, J. ; Kluver, N. ; Schirmer, K. ; Tanneberger, K. ; Tobor-Kaplon, M. ; Witters, H. ; Belanger, S. ; Benfenati, E. ; Creton, S. ; Cronin, M.T.D. ; Eggen, R.I.L. ; Embry, M. ; Ekman, D. ; Gourmelon, A. ; Halder, M. ; Hardy, B. ; Hartung, T. ; Hubesch, B. ; Jungmann, D. ; Lampi, M.A. ; Lee, L. van; Leonard, M. ; Kuster, E. ; Lillicrap, A. ; Luckenbach, T. ; Murk, A.J. ; Navas, J.M. ; Peijnenburg, W. ; Repetto, G. ; Salinas, E. ; Schuurmann, G. ; Spielmann, H. ; Tollefsen, K.E. ; Walter-Rohde, S. ; Whale, G. ; Wheeler, J.R. ; Winter, M.J. - \ 2013
    Regulatory Toxicology and Pharmacology 67 (2013). - ISSN 0273-2300 - p. 506 - 530.
    zebrafish danio-rerio - plant-protection products - messenger-rna expression - adverse outcome pathways - acute fish toxicity - in-vitro - toxicological concern - disrupting chemicals - aquatic toxicity - aromatic-hydrocarbons
    Tests with vertebrates are an integral part of environmental hazard identification and risk assessment of chemicals, plant protection products, pharmaceuticals, biocides, feed additives and effluents. These tests raise ethical and economic concerns and are considered as inappropriate for assessing all of the substances and effluents that require regulatory testing. Hence, there is a strong demand for replacement, reduction and refinement strategies and methods. However, until now alternative approaches have only rarely been used in regulatory settings. This review provides an overview on current regulations of chemicals and the requirements for animal tests in environmental hazard and risk assessment. It aims to highlight the potential areas for alternative approaches in environmental hazard identification and risk assessment. Perspectives and limitations of alternative approaches to animal tests using vertebrates in environmental toxicology, i.e. mainly fish and amphibians, are discussed. Free access to existing (proprietary) animal test data, availability of validated alternative methods and a practical implementation of conceptual approaches such as the Adverse Outcome Pathways and Integrated Testing Strategies were identified as major requirements towards the successful development and implementation of alternative approaches. Although this article focusses on European regulations, its considerations and conclusions are of global relevance
    Smart Agri-Food Logistics: Requirements for the Future Internet
    Verdouw, C.N. ; Sundmaeker, H. ; Meyer, F. ; Wolfert, J. ; Verhoosel, J. - \ 2013
    In: Dynamics in Logistics / Kreowski, Hans-Jörg, Scholz-Reiter, Bernd, Thoben, Klaus-Dieter, Berlin Heidelberg : Springer-Verlag (Lecture Notes in Logistics ) - ISBN 9783642359651 - p. 247 - 257.
    The food and agribusiness is an important sector in European logistics with a share in the EU road transport of about 20 %. One of the main logistic challenges in this sector is to deal with the high dynamics and uncertainty in supply and demand. This paper defines requirements on Future Internet (FI) technologies that have to be met to accomplish the specific challenges of agri-food logistics. It identifies a set of generic technical enablers as input for the realisation of a FI core platform. This technology foundation is to be developed and tested in a Future Internet public–private partnership (FI-PPP) environment of over 150 organisations.
    Refined hazard characterization of 3-MCPD using benchmark dose modeling
    Rietjens, I.M.C.M. ; Scholz, G. ; Berg, I. van den; Schilter, B. ; Slob, W. - \ 2012
    European Journal of Lipid Science and Technology 114 (2012)10. - ISSN 1438-7697 - p. 1140 - 1147.
    3-monochloropropane-1,2-diol 3-mcpd - edible oils - in-vivo - esters - mutagenicity - 3-chloropropane-1,2-diol - exposure - acid - food
    3-Monochloropropane-1,2-diol (3-MCPD)-esters represent a newly identified class of food-borne process contaminants of possible health concern. Due to hydrolysis 3-MCPD esters constitute a potentially significant source of free 3-MCPD exposure and their preliminary risk assessment was based on toxicological data on free 3-MCPD. 3-MCPD is a non-genotoxic carcinogen and a (provisional maximum) tolerable daily intake ((PM)TDI) of 2 mu g/kg bodyweight per day was established by the Scientific Committee on Food and the Joint FAO/WHO Expert Committee on Food Additives. Both committees derived the TDI from a lowest observed adverse effect level, not a no observed adverse effect level, for renal tubular hyperplasia, using an uncertainty factor of 500. When using the Benchmark Dose (BMD) approach and a BMDL10 value as point of departure, part of this uncertainty factor of 500 would no longer be needed. The present study presents a BMD analysis of the currently available chronic data on 3-MCPD mediated induction of tubular hyperplasia in rats as the most sensitive endpoint. The results indicate a (model-averaged) BMDL10 value of 0.72 mg/kg bw/day. The TDI that would be derived based on this BMDL10 value will depend on the uncertainty factor chosen. Using the default uncertainty factor of 100 for inter- and intraspecies extrapolation would result in a TDI of 7 mu g/kg bw/day.
    Matrix Modulation of the Bioactivation of Estragole by Constituents of Different Alkenylbenzene-containing Herbs and Spices and Physiologically Based Biokinetic Modeling of Possible In Vivo Effects
    Al-Husainy, W.A.A.M. ; Berg, S.J.P.L. van den; Paini, A. ; Campana, A. ; Asselman, M. ; Spenkelink, A. ; Punt, A. ; Scholz, G. ; Schilter, B. ; Adams, T.B. ; Bladeren, P.J. van; Rietjens, I. - \ 2012
    Toxicological sciences 129 (2012)1. - ISSN 1096-6080 - p. 174 - 187.
    p-form phenolsulfotransferase - potent inhibitors - interaction threshold - drug-metabolism - dna-adducts - mouse-liver - flavonoids - rats - 1'-hydroxyestragole - quercetin
    The alkenylbenzene estragole is a constituent of several herbs and spices. It induces hepatomas in rodents at high doses following bioactivation by cytochrome P450s and sulfotransferases (SULTs) giving rise to the ultimate carcinogenic metabolite 1'-sulfooxyestragole which forms DNA adducts. Methanolic extracts from different alkenylbenzene-containing herbs and spices were able to inhibit SULT activity. Flavonoids including quercetin, kaempferol, myricetin, apigenin, and nevadensin were the major constituents responsible for this inhibition with Ki values in the nano to micromolar range. In human HepG2 cells exposed to the proximate carcinogen 1'-hydroxyestragole, the various flavonoids were able to inhibit estragole DNA adduct formation and shift metabolism in favor of glucuronidation which is a detoxification pathway for 1'-hydroxyestragole. In a next step, the kinetics for SULT inhibition were incorporated in physiologically based biokinetic (PBBK) models for estragole in rat and human to predict the effect of co-exposure to estragole and (mixtures of) the different flavonoids on the bioactivation in vivo. The PBBK-model-based predictions indicate that the reduction of estragole bioactivation in rat and human by co-administration of the flavonoids is dependent on whether the intracellular liver concentrations of the flavonoids can reach their Ki values. It is expected that this is most easily achieved for nevadensin which has a Ki value in the nanomolar range and is, due to its methyl ation, more metabolically stable than the other flavonoids.
    In vivo validation of DNA adduct formation by estragole in rats predicted by physiologically based biodynamic modelling
    Paini, A. ; Punt, A. ; Scholz, G. ; Gremaud, E. ; Spenkelink, A. ; Alink, G.M. ; Schilter, B. ; Bladeren, P.J. van; Rietjens, I. - \ 2012
    Mutagenesis 27 (2012)6. - ISSN 0267-8357 - p. 653 - 663.
    post-labeling analysis - naturally-occurring alkenylbenzenes - tandem mass-spectrometry - species-differences - drug-metabolism - mouse-liver - 1'-hydroxyestragole - glucuronidation - bioactivation - safrole
    Estragole is a naturally occurring food-borne genotoxic compound found in a variety of food sources, including spices and herbs. This results in human exposure to estragole via the regular diet. The objective of this study was to quantify the dose-dependent estragoleDNA adduct formation in rat liver and the urinary excretion of 1'-hydroxyestragole glucuronide in order to validate our recently developed physiologically based biodynamic (PBBD) model. Groups of male outbred Sprague Dawley rats (n = 10, per group) were administered estragole once by oral gavage at dose levels of 0 (vehicle control), 5, 30, 75, 150, and 300mg estragole/kg bw and sacrificed after 48h. Liver, kidney and lungs were analysed for DNA adducts by LC-MS/MS. Results obtained revealed a dose-dependent increase in DNA adduct formation in the liver. In lungs and kidneys DNA adducts were detected at lower levels than in the liver confirming the occurrence of DNA adducts preferably in the target organ, the liver. The results obtained showed that the PBBD model predictions for both urinary excretion of 1'-hydroxyestragole glucuronide and the guanosine adduct formation in the liver were comparable within less than an order of magnitude to the values actually observed in vivo. The PBBD model was refined using liver zonation to investigate whether its predictive potential could be further improved. The results obtained provide the first data set available on estragoleDNA adduct formation in rats and confirm their occurrence in metabolically active tissues, i.e. liver, lung and kidney, while the significantly higher levels found in liver are in accordance with the liver as the target organ for carcinogenicity. This opens the way towards future modelling of dose-dependent estragole liver DNA adduct formation in human.
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