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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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.
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Summary: Xpaths is a collection of algorithms that allow for the prediction of compound-induced molecular mechanisms of action by integrating phenotypic endpoints of different species; and proposes follow-up tests for model organisms to validate these pathway predictions. The Xpaths algorithms are applied to predict developmental and reproductive toxicity (DART) and implemented into an in silico platform, called DARTpaths.
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Dit rapport is een samenvatting van de volgende onderzoeken: De invloed van huisvesting op de reproductie van de meeltor De invloed van verschillende voedertypes bij het opkweken van meelwormen.
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Net als de eerste editie laat ook deze editie van het rapport met cijfers over 2010 zien dat de gezelschapsdierensector niet zonder maatschappelijke betekenis is. Dit blijkt niet eens zozeer uit de economische waarde van drie miljard euro die het rapport noemt (het bruto binnenlands product was in 2010 bijna 600 miljard euro) maar meer uit het aantal mensen dat in aanraking komt met huisdieren. Het aandeel huishoudens met een of meer huisdieren bedroeg in 2010 ongeveer 59%. De sector geeft werk aan naar schatting 18.000 fte's. Veel banen zijn echter parttime en er zijn veel vrijwilligers werkzaam in de sector. Volgens het rapport is zowel het aantal honden als het aantal katten ten opzichte van 2005 gedaald. Met uitzondering van de knaagdieren worden ook alle andere diersoorten minder als huisdier gehouden. Het rapport beschrijft verder de omvang van allerlei activiteiten die in de sector plaatsvinden.
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Predation risk is a major driver of the distribution of prey animals, which typically show strong responses to cues for predator presence. An unresolved question is whether naïve individuals respond to mimicked cues, and whether such cues can be used to deter prey. We investigated whether playback of wolf sounds induces fear responses in naïve ungulates in a human-dominated landscape from which wolves have been eradicated since 1879. We conducted a playback experiment in mixed-coniferous and broadleaved forest that harboured three cervid and one suid species. At 36 locations, we played wolf sounds, sounds of local sheep or no sounds, consecutively, in random order, and recorded visit rate and group size, using camera traps. Visit rates of cervids and wild boar showed a clear initial reduction to playback of both wolf and sheep sounds, but the type of response differed between sound, forest type and species. For naïve wild boar in particular, responses to predator cues depended on forest type. Effects on visit rate disappeared within 21 days. Group sizes in all the species were not affected by the sound treatment. Our findings suggest that the responses of naïve ungulates to wolf sound seem to be species specific, depend on forest type and wear off in time, indicating habituation. Before we can successfully deter ungulates using predator sound, we should further investigate how different forest types affect the perception of naïve ungulates to these sounds, as responses to predator sound may depend on habitat characteristics.
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