Academic literature on the topic 'Microbial-based toxicity assay'

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Journal articles on the topic "Microbial-based toxicity assay"

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Sarver, Jeffrey G., Jill A. Trendel, Nicole R. Bearss, et al. "Early Stage Efficacy and Toxicology Screening for Antibiotics and Enzyme Inhibitors." Journal of Biomolecular Screening 17, no. 5 (2012): 673–82. http://dx.doi.org/10.1177/1087057112438769.

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The rise in organisms resistant to existing drugs has added urgency to the search for new antimicrobial agents. Aspartate β-semialdehyde dehydrogenase (ASADH) catalyzes a critical step in an essential microbial pathway that is absent in mammals. Our laboratory is using fragment library screening to identify efficient and selective ASADH inhibitors. These preliminary agents are then tested to identify compounds with desired antimicrobial properties for further refinement. Toward this end, we have established a microplate-based, dual-assay approach using a single reagent to evaluate antibiotic activity and mammalian cell toxicity during early stage development. The bacterial assay uses nonpathogenic bacteria to allow efficacy testing without a dedicated microbial laboratory. Toxicity assays are performed with a panel of mammalian cells derived from representative susceptible tissues. These assays can be adapted to target other microbial systems, such as fungi and biofilms, and additional mammalian cell lines can be added as needed. Application of this screening approach to antibiotic standards demonstrates the ability of these assays to identify bacterial selectivity and potential toxicity issues. Tests with selected agents from the ASADH inhibitor fragment library show some compounds with antibiotic activity, but as expected, most of these early agents display higher than desired mammalian cell toxicity.
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Laue, Heike, Lu Hostettler, Gordon Sanders, Georg Kreutzer, and Andreas Natsch. "PeBiToSens™: A Platform for PBT Screening of Fragrance Ingredients Without Animal Testing." CHIMIA International Journal for Chemistry 74, no. 3 (2020): 168–75. http://dx.doi.org/10.2533/chimia.2020.168.

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The determination of persistence (P), bioaccumulation (B) and toxicity (T) plays a central role in the environmental assessment of chemicals. Persistence is typically evaluated via standard microbial biodegradation tests. Bioaccumulation refers to the accumulation of chemicals in organisms and is usually assessed in fish exposed to the test chemical. Toxicity is determined at three trophic levels, with fish toxicity as the highest trophic level assessed. Thus, animal tests are classically needed for both B and T assessment. In vitro systems based on fish liver cells or liver S9 fractions ('RT-S9 assay') have been recently adopted by OECD to measure the biotransformation rates for the chemicals for B assessment. Biotransformation drives clearance from the body and reduces bioaccumulation. For T assessment, an assay based on in vitro toxicity on fish gill cells has been established ('RTgill-W1 assay'). Here we summarize our findings indicating that these tests are highly predictive for fragrance ingredients, and show with two case studies of our latest new registered substances how we apply these tests in particular during development and also for chemical registration. This platform of tests (PeBiToSens™) could fully replace animal tests in ecotoxicological assessment and is key in the Givaudan Safe by Design™ approach to develop safer and environmentally compatible novel fragrance ingredients.
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Philus, Chris Daniel, and Biswanath Mahanty. "Dynamic modelling of tetrazolium-based microbial toxicity assay—a parametric proxy of traditional dose-response relationship." Environmental Science and Pollution Research 28, no. 33 (2021): 45390–401. http://dx.doi.org/10.1007/s11356-021-13870-1.

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Nałęcz-Jawecki, Grzegorz, Jakub Mielniczek, Milena Wawryniuk, Joanna Giebułtowicz, and Agata Drobniewska. "The Microbial Assay for Risk Assessment (MARA) in the Assessment of the Antimicrobial Activity of Ofloxacin and Its Photoproducts." International Journal of Molecular Sciences 26, no. 6 (2025): 2595. https://doi.org/10.3390/ijms26062595.

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Ofloxacin is one of the most commonly used antibacterial substances in the world. Like most medicines, it ends up in the environment through municipal sewage and undergoes various transformations, e.g., photodegradation. The aim of this study was an extensive analysis of ofloxacin photodegradation in both pure antibiotic and a commercial eye drop forms. In this study, a sunlight simulator, chromatographic methods of quantitative and qualitative determination, and biological methods for the evaluation of toxicity (Microbial Assay for Risk Assessment (MARA), Microtox® and Spirotox) were used. The results showed that ofloxacin decomposed almost completely over 2 h of irradiation. Based on the high resolution mass spectrometry, 22 photoproducts were identified. The most sensitive strain of bacteria in the MARA test (Delftia acidovorans) responded at a concentration of 7.6 µg L−1 of ofloxacin. The antibacterial activity of the irradiated samples was higher than that predicted based on the ofloxacin concentration. This suggests that the resulting photoproducts may have a bacteriostatic effect. The results of additional acute toxicity tests indicate the formation of toxic photoproducts, so it is reasonable to use other organisms that are not focused on a specific target. Such actions may allow for the capture of other, unexpected effects of formed photoproducts.
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Papadopoulou, Maria V., William D. Bloomer, Howard S. Rosenzweig, et al. "Nitrotriazole- and Imidazole-Based Amides and Sulfonamides as Antitubercular Agents." Antimicrobial Agents and Chemotherapy 58, no. 11 (2014): 6828–36. http://dx.doi.org/10.1128/aac.03644-14.

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ABSTRACTTwenty-three 3-nitrotriazole-based and 2-nitroimidazole-based amides and sulfonamides were screened for antitubercular (anti-TB) activity in aerobicMycobacterium tuberculosisH37Rv by using the BacTiter-Glo (BTG) microbial cell viability assay. In general, 3-nitrotriazole-based sulfonamides demonstrated anti-TB activity, whereas 3-nitrotriazole-based amides and 2-nitroimidazole-based amides and sulfonamides were inactive. Three 3-nitrotriazole-based sulfonamides (compounds 4, 2, and 7) demonstrated 50% inhibitory concentration (IC50), IC90, and MIC values of 0.38, 0.43, and 1.56 μM (compound 4), 0.57, 0.98, and 3.13 μM (compound 2), and 0.79, 0.87, and 3.13 μM (compound 7), respectively. For 3-nitrotriazole-based sulfonamides, anti-TB activity increased with lipophilicity, whereas the one-electron reduction potential (E1/2) did not play a role. 2-Nitroimidazole-based analogs, which were inactive in the BTG assay, were significantly more active in the low-oxygen assay and more active than the 3-nitrotriazoles. All active nitrotriazoles in the BTG assay were similarly active or more potent (lower MIC values) against resistant strains, with the exception of compounds 2, 3, 4, and 8, which demonstrated greater MIC values against isoniazid-resistant strains. Five 3-nitrotriazole-based sulfonamides demonstrated activity in infected murine J774 macrophages, causing log reductions similar to those seen with rifampin. However, some compounds caused toxicity in uninfected macrophages. In conclusion, the classes of 3-nitrotriazole-based amides and sulfonamides merit further investigation as potential antitubercular agents.
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Nnawuike, Azorji John Paul, Angela Chika Udebuani, Nwachukwu Udodi Chibuike, et al. "Ecological risk evaluation of spent engine oil pollution using earthworm and microbial bioassays." Sustinere: Journal of Environment and Sustainability 8, no. 1 (2024): 91–102. http://dx.doi.org/10.22515/sustinere.jes.v8i1.382.

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The study aimed to assess the ecotoxicological risk associated with the indiscriminate disposal of spent engine oil on terrestrial ecosystem using earthworm and microbial assays. Soil samples were collected from a depth of 0-20 cm and subjected to standard analytical protocols for analysis. Earthworms (assessed by mortality rate) and microorganisms (evaluated for inhibitory effects) covered a wide range of short-term lethal and sub-lethal endpoints used for risk characterization, analyzed through Probit analysis. The result of acute toxicity assay revealed that microbial absorbance rated depended on the dose and type of organism, ranking in the order: Acinetobacter > Enterobacter > Bacillus species >Pseudomonas. Aas oil concentratoin increase, mortality among earthworm was observed. Risk Quotient (RQ) values for Zea mays, Vigna unguiculata, Glycine max and earthworm varied from low to very high risk based on estimated Predicted No Effect Concentration (PNEC) values. Microorganisms exhibited differing level of biotolerance to spent engine oil exposure as indicated by respective risk quotient values. Exposure to spent engine oil posed minimal risk to Pseudomonas sp., Bacillus sp., and Acinetobacter sp., with RQ values below unity (< 1). Conversely, Enterobacter sp. Showed a high risk with values above unity. Earthworms play a pivotal role in agriculture due to their numerous economic benefots. Soil microorganisms are essential for maintening soil quality by performing vital processes. The antimicrobial properties of spent engine oil on soil may distort microbial activities, potentially inhibiting their growth and leading to alterations in ecological functionality of the soil.
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Alothman, Zeid A., Ali H. Bahkali, Abdallah M. Elgorban, et al. "Bioremediation of Explosive TNT by Trichoderma viride." Molecules 25, no. 6 (2020): 1393. http://dx.doi.org/10.3390/molecules25061393.

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Nitroaromatic and nitroamine compounds such as 2,4,6-trinitrotoluene (TNT) are teratogenic, cytotoxic, and may cause cellular mutations in humans, animals, plants, and microorganisms. Microbial-based bioremediation technologies have been shown to offer several advantages against the cellular toxicity of nitro-organic compounds. Thus, the current study was designed to evaluate the ability of Trichoderma viride to degrade nitrogenous explosives, such as TNT, by microbiological assay and Gas chromatography–mass spectrometry (GC–MS) analysis. In this study, T. viride fungus was shown to have the ability to decompose, and TNT explosives were used at doses of 50 and 100 ppm on the respective growth media as a nitrogenous source needed for normal growth. The GC/MS analysis confirmed the biodegradable efficiency of TNT, whereas the initial retention peak of the TNT compounds disappeared, and another two peaks appeared at the retention times of 9.31 and 13.14 min. Mass spectrum analysis identified 5-(hydroxymethyl)-2-furancarboxaldehyde with the molecular formula C6H6O3 and a molecular weight of 126 g·mol−1 as the major compound, and 4-propyl benzaldehyde with a formula of C10H12O and a molecular weight of 148 g mol−1 as the minor compound, both resulting from the biodegradation of TNT by T. viride. In conclusion, T. viride could be used in microbial-based bioremediation technologies as a biological agent to eradicate the toxicity of the TNT explosive. In addition, future molecular-based studies should be conducted to clearly identify the enzymes and the corresponding genes that give T. viride the ability to degrade and remediate TNT explosives. This could help in the eradication of soils contaminated with explosives or other toxic biohazards.
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Almeida, Anna C., Viviane A. Andrade, Francine S. A. Fonseca, et al. "Acute and chronic toxicity and antimicrobial activity of the extract of Stryphnodendron adstringens (Mart.) Coville." Pesquisa Veterinária Brasileira 37, no. 8 (2017): 840–46. http://dx.doi.org/10.1590/s0100-736x2017000800010.

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ABSTRACT: This study evaluated the antimicrobial activity and acute or chronic toxicity of the extract of Stryphnodendron adstringens. The stem bark dry extract was obtained by static maceration with ethanol. Quantification of tannins was performed by the Folin-Denis method, which indicated a total tannin content of 32.7%. The antimicrobial activity of the dry extract of S. adstringens was evaluated by agar-based disk diffusion assay with Escherichia coli (ATCC 25922) and Staphylococcus aureus (ATCC 25923) in the concentration of 200, 400 and 600μL/mL. The results indicated that 600μL/mL inhibited microbial growth, i.e. had antimicrobial activity against these species. Acute and chronic toxic effects of S. adstringens was evaluated in Wistar rats treated with 200, 400, 600 and 800mg/kg of extract, administrated by gavage. Liver degeneration was observed in the group of rats receiving 800mg/kg in chronic exposure, what may indicate some degree of toxicity at this concentration. However, no systemic toxicity was observed at lower doses. Considering the broad use of S. adstringens as a phytotherapeutic agent for various human and animal diseases and the livertoxicity observed at high concentrations, attention should be paid to the possible adverse effect of using the extract from this plant at high concentration.
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Smith, Kenneth P., Matthew G. Dowgiallo, Lucius Chiaraviglio, et al. "A Whole-Cell Screen for Adjunctive and Direct Antimicrobials Active against Carbapenem-Resistant Enterobacteriaceae." SLAS DISCOVERY: Advancing the Science of Drug Discovery 24, no. 8 (2019): 842–53. http://dx.doi.org/10.1177/2472555219859592.

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Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging antimicrobial resistance threat for which few if any therapeutic options remain. Identification of new agents that either inhibit CRE or restore activity of existing antimicrobials is highly desirable. Therefore, a high-throughput screen of 182,427 commercially available compounds was used to identify small molecules which either enhanced activity of meropenem against a carbapenem-resistant Klebsiella pneumoniae ST258 screening strain and/or directly inhibited its growth. The primary screening methodology was a whole-cell screen/counterscreen combination assay that tested for reduction of microbial growth in the presence or absence of meropenem, respectively. Screening hits demonstrating eukaryotic cell toxicity based on an orthogonal screening effort or identified as pan-assay interference compounds (PAINS) by computational methods were triaged. Primary screening hits were then clustered and ranked according to favorable physicochemical properties. Among remaining hits, we found 10 compounds that enhanced activity of carbapenems against a subset of CRE. Direct antimicrobials that passed toxicity and PAINS filters were not, however, identified in this relatively large screening effort. It was previously shown that the same screening strategy was productive for identifying candidates for further development when screening known bioactive libraries inclusive of natural products. Our findings therefore further highlight liabilities of commercially available small-molecule screening libraries in the Gram-negative antimicrobial space. In particular, there was especially low yield in identifying compelling activity against a representative, highly multidrug-resistant, carbapenemase-producing K. pneumoniae strain.
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Tabaika, Pryandi M., Sri Dewi Astuty, Syamsir Dewang, Nur Umriani Permatasari, and Wahiduddin Wahiduddin. "The Comparison between Energy Density of Blue and Red Light which Activation Silver Nanoparticles to Inhibition Candida albicans Biofilms." Trends in Sciences 21, no. 8 (2024): 7702. http://dx.doi.org/10.48048/tis.2024.7702.

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Photodynamic inactivation (PDI) is a technique to inhibit microbial biofilm growth through the toxicity of Reactive Oxygen Species (ROS) compounds. ROS can be attack membrane, lipids, DNA and nucleic acid then initiate cell necrosis. This study aims to analyze the potential of red and blue LEDs to activating silver nanoparticles (AgNPs) to produce significant amounts of ROS that are believed to be toxic and lethal to Candida albicans biofilm cells. The effectiveness of the treatment in this study was evaluated through cell viability represented by Optical Density values and malondialdehyde levels. There were 4 treatment groups used as samples, namely the control group, the photosensitizer group, the light group, and the combination group of light with photosensitizer. The duration of light exposure ranged from 2 to 10 min with a power of 100 MW. The biofilm staining done to detection some indicator as an impact of photodynamic against mortality and survive cell with 2 dyes are XTT assay as cell viability values and the Thiobarbituric Acid Reactive Substances assay for malondialdehyde levels. The results showed that photoinactivation of Candida albicans biofilm with the lowest viability occurred in the treatment group of the combination of blue light with AgNPs with an irradiation duration of 10 min, namely 0.076 ± 0.005 and the treatment group of the combination of red light with AgNPs with an irradiation duration of 10 min, namely 0.131 ± 0.021. The data resulted in an inactivation rate of 94.68 ± 0.55 % for blue light and 90.98 ± 0.02 % for red light. The malondialdehyde levels were 1.563 nmol/mL for blue light and 1.514 nmol/mL for red light. The comparison of blue light treatment with red light is based on penetration in the cell, where blue light has low penetration but high energy which gives more opportunities to produce ROS at the triplet level. The combination of blue LED spectrum with AgNPs is highly effective in inactivating the metabolic activity of pathogenic microbial cells. HIGHLIGHTS Candida albicans biofilm is very rigid and has strong potential as a chronic infection. The research focuses on the application of photodynamic inactivation with LED light and antimicrobial AgNPs. Identification of the results with XTT assay 94.65 % inhibition and TBARS assay at MDA level of 1,864 nmol/mL. GRAPHICAL ABSTRACT
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Dissertations / Theses on the topic "Microbial-based toxicity assay"

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Catterall, Kylie. "Development of a Rapid Microbial-Based Toxicity Assay Employing Ferricyanide as an Artificial Respiratory Electron Acceptor." Thesis, Griffith University, 2007. http://hdl.handle.net/10072/367811.

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The use of ferricyanide-mediated microbial reactions was investigated with a view to developing a rapid microbial-based toxicity assay to overcome the short falls of existing techniques currently employed in the water and wastewater industry. This assay, known as the ferricyanide-mediated toxicity (FMTOX) assay, employs ferricyanide in place of oxygen as an artificial electron acceptor during microbial respiration. The principle behind this assay is similar to conventional microbial-based toxicity assays that quantify the inhibition of the electron transport system of microorganisms. In this case, however, rather than monitoring changes in bioluminescence (Microtox), oxygen (OEeD 209 Activated Sludge Respiration Inhibition Assay) or the production of oxidised nitrogen (ISO 9509 Activated Sludge Nitrification Inhibition Assay), the FMTOX assay quantifies microbially produced ferrocyanide derived from ferricyanide cellular respiration using an electrochemical detection system. In order to ascertain the relevance and practicality of the newly developed FMTOX assay, a tool box was developed that included a list features that an ideal microbialbased toxicity assay would have when applied to the water and wastewater industry. An assessment of other available microbial-based toxicity assays against the ideal toxicity assay was also made. Throughout this study, the use of this tool box approach served as a means to direct systematic research on FMTOX development and optimisation and also to evaluate if this new assay improves on the currently available microbial toxicity assays. FMTOX method validation, proof of concept investigations and optimisation of key experimental parameters was facilitated employing, Escherichia coli and 3,5-Dichlorophenol (3,5-DCP) as a model microorganism and test substance respectively. Following a concentration-response experimental design using a range of organic and inorganic test substances, the versatility of the generic FMTOX assay developed using E. coli was successfully applied without further modification (excluding exposure temperature) to three other microbial test species (Pseudomonas jluorescens, Bacillus subtilis and Acetobacter calcoaceticus). Furthermore, when a test substance exerted a measurable inhibitory effect, the trends obtained were found to display classic sigmoid shaped concentration-response curves reported for conventional toxicity assays. The degree of similarity between the ranked IC50 values calculated for the FMTOX microorganisms and literature values reported for standard microbial-based toxicity assays were compared using the Bray Curtis similarity matrix and visually displayed using hierarchal cluster analysis. While the trends obtained revealed that each of the microorganisms within the assays have their own sensitivity profiles, some similarities were evident. For example, of the microorganisms investigated in the FMTOX assay, B. subtilis was generally found to be the most sensitive test microorganism and the toxicity profiles obtained were found to be 88% similar to the ranked IC50 values reported for the Microtox assay. Consequently, it was proposed that the FMTOX B. subtilis assay would be relevant for applications where the Microtox assay has been typically employed, such as those requiring high sensitivity. On the other hand, owing to generally higher IC50 values, the FMTOX assay using A. calcoaceticus was found to be more comparable the activated sludge based assays as evidenced by relatively high percent similarities (93%) for both the OECD 209 assay and the ISO 9509 assay. It was therefore suggested that FMTOX A. calcoaceticus would be more suitable for applications where the activated sludge based toxicity assays are employed, such as WWTP influent monitoring, WWTP process control, and compliance monitoring of industries discharging into sewers. The successful application of the single microorganisms in the FMTOX assay prompted the investigation and development of a FMTOX assay employing activated sludge obtained from a WWTP. The results of this investigation are significant for a number of reasons. Firstly, this is the first report that has demonstrated that a mixed microbial consortium of activated sludge is able to reduce the artificial electron acceptor, ferricyanide, to ferrocyanide during cellular respiration. Secondly, using the test substances employed for the FMTOX single microorganisms, 97% (45 and 75 minutes total exposure times) and 100% similarity (135 minute total exposure time) in the ranked IC50 values were found between the OECD 209 assay and the FMTOX activated sludge. Comparison with the ISO 9509 assay also yielded excellent agreement as percent similarities ranging from 87% to 90% were found for each of the three FMTOX activated sludge assay exposure times. Importantly, the FMTOX activated sludge assay was able to achieve these comparable results in a much faster time frame (45 min.-135 min.) compared to the OECD 209 assay (3 hours) and the ISO 9509 assay (4 hours). Finally, the FMTOX activated sludge assay was also found to be much simpler to perform and required significantly reduced preparation and analysis time. Based on these very promising results it was concluded that the FMTOX assay employing activated sludge assay would be more appropriate for assessing the impact of wastewaters to the specific activated sludge community inhabiting any WWTP. The flexibility of being able to modify the biocatalyst(s) in the FMTOX assay demonstrates the versatility of the assay as it means that biocatalysts can be selected based on the indigenous species present in the environment being monitored and/or on the sensitivity and selectivity profiles required for specific applications. Importantly, this flexibility together with other significant advantages means that the FMTOX assay shows the necessary attributes of an ideal microbial-based toxicity assay that would be relevant to a wide variety of applications in the water and wastewater industry. Nevertheless, it is acknowledged that additional developmental work is still required, such as, analysis of the day to day variability of the FMTOX assay, further investigations of more test microorganisms, including tailor made mixed microbial consortiums and test batteries; further investigations of more test substances including mixtures and real samples; and further investigations of possible interferences to the FMTOX detection system.<br>Thesis (PhD Doctorate)<br>Doctor of Philosophy (PhD)<br>School of Environmental and Applied Science<br>Full Text
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Gladman, Calvin. "Ferricyanide Mediated Microbial Respiration - Application to the Analysis of Waters and Wastewaters." Thesis, Griffith University, 2011. http://hdl.handle.net/10072/367669.

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A novel rapid respiration-based bioassay for the quantitative determination of microbial oxidation of organic substrate in wastewaters has been developed. By replacing oxygen as the terminal electron acceptor with the ferricyanide ion during microbial respiration, the rate and extent of the biochemical reaction (i.e. oxidation of substrate) was significantly increased. This was due to the high solubility of the ferricyanide ion in solution, thereby allowing the use of substantially larger populations of microorganisms in the assay without rapid depletion of the electron acceptor during respiration. The ferricyanide mediated respiration (FM-Res) assay was successfully employed as a platform for the further development of both a rapid biochemical oxygen demand (FM-BOD) and rapid toxicity assay (FM-Tox). Under ferricyanide mediated conditions, both assay types exhibited biochemical behaviour analogous to where oxygen would typically act as a terminal electron acceptor, effectively establishing proof of concept. Optimisation of the biocatalyst in the FM-Res assay showed that a broad range of phylogenetically diverse microorganisms were able to utilise the ferricyanide ion as an alternative electron acceptor in the biodegradation of a wide range of organic compounds. The most suitable type of biocatalyst for use in the FM-Res assay was shown to be a mixed microbial consortium capable of degrading large amounts and types of compounds. In the case of the FM-BOD assay, the use of a mixed microbial consortium substantially increased the dynamic linear working range when compared to more traditional methods of analysis such as BOD5.<br>Thesis (PhD Doctorate)<br>Doctor of Philosophy (PhD)<br>Griffith School of Environment<br>Science, Environment, Engineering and Technology<br>Full Text
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