From the article: "To enable selection of novel chemicals for new processes, there is a recognized need for alternative toxicity screening assays to assess potential risks to man and the environment. For human health hazard assessment these screening assays need to be translational to humans, have high throughput capability, and from an animal welfare perspective be harmonized with the principles of the 3Rs (Reduction, Refinement, Replacement). In the area of toxicology a number of cell culture systems are available but while these have some predictive value, they are not ideally suited for the prediction of developmental and reproductive toxicology (DART). This is because they often lack biotransformation capacity, multicellular or multi- organ complexity, for example, the hypothalamus pituitary gonad (HPG) axis and the complete life cycle of whole organisms. To try to overcome some of these limitations in this study, we have used Caenorhabditis elegans (nematode) and Danio rerio embryos (zebrafish) as alternative assays for DART hazard assessment of some candidate chemicals being considered for a new commercial application. Nematodes exposed to Piperazine and one of the analogs tested showed a slight delay in development compared to untreated animals but only at high concentrations and with Piperazine as the most sensitive compound. Total brood size of the nematodes was also reduced primarily by Piperazine and one of the analogs. In zebrafish Piperazine and analogs showed developmental delays. Malformations and mortality in individual fish were also scored. Significant malformations were most sensitively identified with Piperazine, significant mortality was only observed in Piperazine and only at the higest dose. Thus, Piperazine seemed the most toxic compound for both nematodes and zebrafish. The results of the nematode and zebrafish studies were in alignment with data obtained from conventional mammalian toxicity studies indicating that these have potential as developmental toxicity screening systems. The results of these studies also provided reassurance that none of the Piperazines tested are likely to have any significant developmental and/or reproductive toxicity issues to humans when used in their commercial applications."
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Potato cyst nematodes (PCN) are in the Northern Netherlands and the Weser-Ems Region in Germany a major issue for farmers. The yearly average damage by PCN is about 100 Euros/hectare for farmers. Infestations of potato cyst nematodes can be controlled in a sustainable way by proper potato variety selection. Potato varieties vary in the degree of tolerance and resistance to PCN. However, this knowledge is used by only a small fraction of the farmers. The AGROBIOKON project, which is funded by the INTERREG EDR-region, the Landwirtschaftskammer Niedersachsen and the Dutch farmers association, have developed a decision support system for potato variety selection based upon population dynamic models for PCN: OPTIRas. The scientific principles and the model behind the decision support system will be presented. The model will be applied to PCN field experiments in the Weser-Ems region. Experience of using this decision support system in farmer study groups in the Netherlands and Germany will be shared.
Implementation of reliable methodologies allowing Reduction, Refinement, and Replacement (3Rs) of animal testing is a process that takes several decades and is still not complete. Reliable methods are essential for regulatory hazard assessment of chemicals where differences in test protocol can influence the test outcomes and thus affect the confidence in the predictive value of the organisms used as an alternative for mammals. Although test guidelines are common for mammalian studies, they are scarce for non-vertebrate organisms that would allow for the 3Rs of animal testing. Here, we present a set of 30 reporting criteria as the basis for such a guideline for Developmental and Reproductive Toxicology (DART) testing in the nematode Caenorhabditis elegans. Small organisms like C. elegans are upcoming in new approach methodologies for hazard assessment; thus, reliable and robust test protocols are urgently needed. A literature assessment of the fulfilment of the reporting criteria demonstrates that although studies describe methodological details, essential information such as compound purity and lot/batch number or type of container is often not reported. The formulated set of reporting criteria for C. elegans testing can be used by (i) researchers to describe essential experimental details (ii) data scientists that aggregate information to assess data quality and include data in aggregated databases (iii) regulators to assess study data for inclusion in regulatory hazard assessment of chemicals.
Aaltjes: automatisch classificeren en tellen. Agrariërs laten bodemmonsters analyseren op onder meer aanwezigheid van aaltjes. Deze bodemanalyse is voor agrariërs cruciaal om de bodemgezondheid- en vruchtbaarheid vast te stellen maar behelst een grote kostenpost. Het identificeren, analyseren en tellen van aaltjes (nematoden) in een bodemmonster geschiedt in een gespecialiseerd laboratorium. Dit is tijdrovend, specialistisch en seizoensgebonden werk. Het tellen- en analyseren van aaltjes is mensenwerk en vergt training en ervaring van de laborant. Daarnaast hebben de laboratoria te maken met personeelstekort en de laboranten met sterk fluctuerende werkdruk. Derhalve is het speciaal voor dit project opgerichte samenwerkingsverband tussen Fontys GreenTechLab, ROBA Laboratorium en CytoSMART voornemens om een oplossing te ontwikkelen voor het automatisch classificeren en tellen van aaltjes. Dit project richt zich op de ontwikkeling van een proof of concept van een analysescanner. Het werk van de laboranten wordt grotendeels geautomatiseerd waarbij door de scanner de bodemmonsters middels toepassing van deep learning en virtual modeling kan worden geanalyseerd. Daarmee wordt beoogd een oplossing te bieden waarmee het personeelstekort wordt tegengegaan, de werkdruk kan worden verlaagd, mensenwerk wordt geautomatiseerd (waardoor de kans op fouten wordt verkleind) en de kosten voor agrariërs worden verlaagd.
An important line of research within the Center of Expertise HAN BioCentre is the development of the nematode Caenorhabditis elegans as an animal testing replacement organism. In the context of this, us and our partners in the research line Elegant! (project number. 2014-01-07PRO) developed reliable test protocols, data analysis strategies and new technology, to determine the expected effects of exposure to specific substances using C. elegans. Two types of effects to be investigated were envisaged, namely: i) testing of possible toxicity of substances to humans; and ii) testing for potential health promotion of substances for humans. An important deliverable was to show that the observed effects in the nematode can indeed be translated into effects in humans. With regard to this aspect, partner Preventimed has conducted research in obesity patients during the past year into the effect of a specific cherry extract that was selected as promising on the basis of the study with C. elegans. This research is currently being completed and a scientific publication will have to be written. The Top Up grant is intended to support the publication of the findings from Elegant! and also to help design experimental protocols that enable students to become acquainted with alternative medical testing systems to reduce the use of laboratory animals during laboratory training.
De nematode C. elegans is als alternatief testsysteem een zeer aantrekkelijk organisme voor het beoordelen van stoffen op potentieel schadelijke effecten. Het biedt door zijn geringe grootte van maar 1 mm een alternatief om op snelle wijze veel stoffen te beoordelen. C. elegans valt als ongewerveld dier niet onder de dierproefwet en kan ongelimiteerd zonder benodigde vergunningen worden ingezet. In de afgelopen jaren is uit gesubsidieerd onderzoek (RAAK MKB, CRACKIT) gebleken dat C. elegans een goede voorspellende waarde heeft om effecten te beoordelen die stoffen mogelijk hebben op de ontwikkeling en reproductie. Via een haalbaarheidsstudie wordt de markt beter in kaart gebracht en een verzelfstandigingsmodel ontwikkeld vor de relatie met de HAN.
