How does defamiliarization relate to that which it assumes to be familiar? This chapter explores this question in the context of toxicity, an often invisible and imperceptible power, with the aid of two case studies from landscape art. Wout Berger’ s work Giflandschap (Poisoned Landscape, 1992) is exemplary of the ways in which defamiliarization has been a useful aesthetic strategy for artists to make toxicity’ s presence in the everyday tangible. But if toxicity (also outside artistic contexts) always has to be discovered or remembered anew, as Lawrence Buell (Toxic Discourse. Critical Inquiry 24(3): 639–665, 1998) already pointed out, how can we learn to live with toxicity and to understand its ongoing, pervasive presence? Can defamiliarization actually stay with the toxic trouble at hand (Haraway, Staying with the Trouble: Making Kin in the Chthulucene. Durham: Duke University Press, 2016)? Through a second case study, Alexandra Navratil’ s Silbersee (2015), this chapter explores the possibilities of getting intimate with toxicity instead. Ultimately, it suggests that in the context of toxicity, it can be generative to make the strange familiar again.
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From the article: Abstract Sub-chronic toxicity studies of 163 non-genotoxic chemicals were evaluated in order to predict the tumour outcome of 24-month rat carcinogenicity studies obtained from the EFSA and ToxRef databases. Hundred eleven of the 148 chemicals that did not induce putative preneoplastic lesions in the sub-chronic study also did not induce tumours in the carcinogenicity study (True Negatives). Cellular hypertrophy appeared to be an unreliable predictor of carcinogenicity. The negative predictivity, the measure of the compounds evaluated that did not show any putative preneoplastic lesion in de sub-chronic studies and were negative in the carcinogenicity studies, was 75%, whereas the sensitivity, a measure of the sub-chronic study to predict a positive carcinogenicity outcome was only 5%. The specificity, the accuracy of the sub-chronic study to correctly identify non-carcinogens was 90%. When the chemicals which induced tumours generally considered not relevant for humans (33 out of 37 False Negatives) are classified as True Negatives, the negative predictivity amounts to 97%. Overall, the results of this retrospective study support the concept that chemicals showing no histopathological risk factors for neoplasia in a sub-chronic study in rats may be considered non-carcinogenic and do not require further testing in a carcinogenicity study.
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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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Relatie tussen spiermassa en vroegtijdig stoppen van chemotherapie bij patienten met hoofd-halskankerIn this study, we aim to assess whether low pre-treatment muscle mass, measured with CT at thoracic (T4) or lumbar level (L3) is associated with early termination of chemotherapy related to toxicity in head and neck cancer (HNC) patients.
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.
Aanleiding Nieuwe stoffen en producten van de farmaceutische sector en de (agro)chemie moeten uitgebreid getest worden voordat ze op de markt kunnen verschijnen. Voor die testen is nu nog een groot aantal proefdieren nodig. Dit stuit echter op een aantal bezwaren: de uitkomsten van deze studies zijn niet altijd goed vertaalbaar naar effecten bij de mens, proefdierstudies zijn duur en de ethische kant van dierproeven staat steeds vaker ter discussie. Bedrijven zijn naarstig op zoek naar alternatieve testsystemen die ervoor kunnen zorgen dat proefdierstudies met zoogdieren worden verminderd, verfijnd en vervangen (de drie V's). Doelstelling In twee eerdere RAAK-projecten is ontdekt dat nematode C. elegans een kansrijk alternatief voor dierproeven is. Het is nu aan het multidisciplinaire team van Elegant! om de potentie van deze rondworm uit te bouwen en te ontwikkelen in een gevalideerd onderzoeksmodel voor de chemische, agrochemische en farmaceutische sector. Zij gaan C. elegans inzetten als alternatief testmodel om complexe responsen te meten. De vragen die zij willen beantwoorden met het onderzoek zijn: " Hoe effectief is het gebruik van C. elegans als alternatief testsysteem in het voorspellen van mogelijke toxische effecten en farmaceutische activiteiten? " In hoeverre kan C. elegans een meerwaarde hebben met betrekking tot het bestuderen en begrijpen van het onderliggende werkingsmechanisme? Beoogde resultaten Het resultaat van het project is kennis over de effectiviteit van C. elegans als alternatief systeem voor het screenen van stoffen op veiligheid en activiteit. Tijdens het onderzoek wordt er ook nieuwe technologie ontwikkeld, waaronder: " een productieproces voor de continue aanlevering van wormen; " lab-on-chipmodule voor high-throughput microscopie; " zelfregulerende mappingtool voor verzameling en interpretatie van data.
