Toxicity Testing in the 21st Century: Challenges and Perspectives

Bluemel, Joerg

doi:10.4172/2157-7609.1000e112

Cited by 2 publications

(2 citation statements)

References 16 publications

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“…With the on-going international shift away from vertebrate animal testing in toxicology, we envision testing in lower animal species will increase substantially in importance. For example, state of the art omics approaches (Bluemel 2012) are beginning to gain support by industry and regulators; such studies conducted on aquatic invertebrates such as Daphnia could utilise a miniaturised high throughput toxicity range finding experiment to first select appropriate exposure concentrations for the subsequent omics investigations.…”

Section: Discussionmentioning

confidence: 99%

Miniaturising acute toxicity and feeding rate measurements in Daphnia magna

Grintzalis

Dai

Panagiotidis

et al. 2017

Ecotoxicology and Environmental Safety

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Phenotypic markers of animal health form an essential component of regulatory toxicology. Immobilisation of neonate water fleas - Daphnia magna - as a surrogate measure of their mortality following exposure to a chemical for 24-48h forms the basis of the internationally utilised OECD acute toxicity test 202. A second important marker of animal physiology and health is feeding rate, which in Daphnia is determined by measuring the algae feeding rate. Given the widespread use of OECD test 202 for acute toxicity as well as the quantification of feeding rate in toxicological studies of daphniids, significant benefits could result from miniaturising this assay. In particular, miniaturisation would use fewer animals, less media and chemicals, less laboratory space and make the tests more compatible with automation, and therefore could result in considerable time savings. Furthermore, miniaturising phenotypic markers to the ultimate level of a single animal per well would facilitate multiple measurements of other phenotypic markers, such as behavioural responses, which could be integrated at the individual level. In this study we used a wide range of exposure vessels to evaluate the impacts of systematically varying total media volume, surface to volume ratio and animal density for the acute toxicity testing of cadmium. We demonstrate that Daphnia acute toxicity tests using single animals within 24- or 48-well plates produce equivalent results as for traditional test configurations, for different chemicals. Considering algae feeding rates by Daphnia, we studied the impacts of varying algae concentration, total volume and animal density. After having demonstrated that multiwell plates can again yield equivalent test results as traditional experimental setups, we used miniaturised test vessels to show the impact of metals on the feeding activity on daphniids for both neonates and adult animals. Overall we confirm the feasibility of a multiwell approach for Daphnia toxicity testing that requires less time and materials than a traditional assay and can provide phenotypic characterisation at a single animal level.

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Section: Discussionmentioning

confidence: 99%

Miniaturising acute toxicity and feeding rate measurements in Daphnia magna

Grintzalis

Dai

Panagiotidis

et al. 2017

Ecotoxicology and Environmental Safety

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“…Toxicity testing is particularly important when whole-cell screens (Tables 1 and 2) have been used for bioprospecting because, with the exception of some cell morphology-based assays and assays using under-expressing, over-expressing or reporter strains of bacteria, these screens do not distinguish between specific (bacterial) and nonspecific (general) cell toxicity (119). The number of in vitro assays available for toxicity testing has grown considerably in recent years and continues to grow, driven by public concern for animal welfare (169,170) and legislative control of animal use (171,172), and a desire on the part of pharmaceutical companies and regulatory agencies to reduce false-negative and false-positive test results caused by species-specific toxicity (173,174), to reduce the cost and duration of toxicity testing (171,175), to generate data for SAR analysis and pharmacokinetic and pharmacodynamic models (176), and to detect toxicity problems earlier in the drug development process (170,177).…”

Section: Toxicity Testingmentioning

confidence: 99%

Bioprospecting for Antibacterial Drugs: a Multidisciplinary Perspective on Natural Product Source Material, Bioassay Selection and Avoidable Pitfalls

Cushnie

Echeverría

et al. 2020

Pharm Res

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Bioprospecting is the exploration, extraction and screening of biological material and sometimes indigenous knowledge to discover and develop new drugs and other products. Most antibiotics in current clinical use (eg. β-lactams, aminoglycosides, tetracyclines, macrolides) were discovered using this approach, and there are strong arguments to reprioritize bioprospecting over other strategies in the search for new antibacterial drugs. Academic institutions should be well positioned to lead the early stages of these efforts given their many thousands of locations globally and because they are not constrained by the same commercial considerations as industry. University groups can lack the full complement of knowledge and skills needed though (eg. how to tailor screening strategy to biological source material).In this article, we review three key aspects of the bioprospecting literature (source material and in vitro antibacterial and toxicity testing) and present an integrated multidisciplinary perspective on (a) source material selection, (b) legal, taxonomic and other issues related to source material, (c) cultivation methods, (d) bioassay selection, (e) technical standards available, (f) extract/compound dissolution, (g) use of minimum inhibitory concentration and selectivity index values to identify progressible extracts and compounds, and (h) avoidable pitfalls. The review closes with recommendations for future study design and information on subsequent steps in the bioprospecting process.

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Toxicity Testing in the 21st Century: Challenges and Perspectives

Cited by 2 publications

References 16 publications

Miniaturising acute toxicity and feeding rate measurements in Daphnia magna

Miniaturising acute toxicity and feeding rate measurements in Daphnia magna

Bioprospecting for Antibacterial Drugs: a Multidisciplinary Perspective on Natural Product Source Material, Bioassay Selection and Avoidable Pitfalls

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