BURA Collection:

Machine learning approaches to understand the uptake and elimination of anthropogenic stressors in animal health

2026-06-18T14:37:31Z

Title: Machine learning approaches to understand the uptake and elimination of anthropogenic stressors in animal health Authors: Uhlhorn, Jasmin Abstract: The detection of pharmaceuticals in aquatic ecosystems raises questions about their potential effects on non-target organisms. However, environmental concentrations do not directly reflect the internal body burden of organisms. As part of this work, an investigation of contaminants of emerging concern in a coastal ecosystem as well as in marine biota highlighted this, with internal and surface water concentrations differing substantially. The gap may be linked to both environmental conditions and compound-specific uptake and elimination processes, which affect their bioaccumulation potential. Laboratory-based studies to understand compound-dependent uptake and elimination kinetics have traditionally focused on fish. In line with the 3Rs principle and regulatory efforts to move away from vertebrate testing, and to broaden taxonomic coverage, this work aimed to assess the potential of the invertebrate model species Daphnia magna to be used in mixture-based exposures as a high-throughput alternative. This necessitated the development and validation of a broad targeted analytical method for the determination of multi-class pharmaceuticals in D. magna, which had not previously been developed. This work successfully developed a method applicable across multiple pharmaceutical classes, capable of quantifying more than 50 compounds to acceptance criteria defined by ICH method validation guidelines. Mixture toxicokinetic exposures were performed, ranging from a single compound to simultaneous exposure of up to 50 compounds, and toxicokinetic profiles were successfully derived for 49 pharmaceuticals. Pharmaceuticals generally exhibited low bioconcentration potential with the majority of compounds having bioconcentration factors (BCFs) of <60 L kg-1 dry weight (dw), yet values ranged from 2 to >10,000 L kg-1 dw. The broad range highlights the importance of considering internal exposure when assessing hazard and subsequent risk. The generated toxicokinetic data was applied to machine learning models alongside published fish BCF data. The models achieved good performance for fish but showed limited predictive ability for D. magna. Mechanistic evaluation confirmed that models identified established properties and relationships that are linked to bioaccumulation and membrane permeability (logP, TPSA), demonstrating their ability to capture relevant processes when sufficient representative data is available. Overall, this work highlighted the potential of mixture-based approaches in the non-vertebrate organism D. magna to enable higher-throughput bioconcentration assessment. Utilising this high-throughput testing could rapidly generate ecotoxicity data to fulfil regulatory requirements and enable in silico modelling approaches to potentially replace animal testing in the future. Description: This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University London

Effects of antidepressant drug pollution on molluscs

2025-06-25T02:01:11Z

Title: Effects of antidepressant drug pollution on molluscs Authors: Imiuwa, Eghosa Maurice Abstract: There are growing concerns molluscs may be more vulnerable to the effects of antidepressant drug pollution than any other animal phylum as a multitude of key physiological processes are regulated by monoamines, the target of antidepressants, in molluscs. However, target-mediated effects of different classes of antidepressants at environmental levels in molluscs remain to be understood as currently existing studies have largely focused on effects of concentrations that are not environmentally relevant. Moreover, the effects of antidepressants on overarching physiological processes such as feeding and reproductive behaviours (shell mounting and intromission) have not been reported in any molluscan species in addition to the absence of report on the effects of two major classes of antidepressant drugs on fecundity in molluscs. Furthermore, according to the read-across hypothesis, pharmacological responses (target-mediated effects) of a pharmaceutical would occur in an organism in which the drug targets are conserved if the plasma concentrations of the pharmaceutical approaches its human therapeutic plasma concentration. Despite this, hemolymph levels of antidepressants have not also been reported in any molluscan species. To address this critical knowledge gap, a systematic review of the literature was conducted; and the effects and hemolymph levels of environmentally relevant concentrations of widely prescribed antidepressant drugs (3 classes) including amitriptyline (10, 100, 500 and 1000 ng/L), fluoxetine (10, 100 and 500 ng/L) and venlafaxine (0.5, 1, 2, 4 and 55 μg/L) in the freshwater mollusc, Biomphalaria glabrata, were investigated over a period of 28 days. The endpoints included feeding, reproduction (fecundity), growth, substrate attachment, spatial distribution, shell mounting and intromission. Feeding and reproduction were disrupted at particularly low hemolymph levels of antidepressants (with venlafaxine being the least potent), while the systematic review reveals that immunosuppression is a major target-mediated effect of antidepressants in molluscs. The study provides novel critical data relevant to regulatory decision-making and future research direction. Description: This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University London

Systematic, molecular, and (eco)toxicology investigations of endocrine mechanisms in molluscs

2025-05-02T02:01:24Z

Title: Systematic, molecular, and (eco)toxicology investigations of endocrine mechanisms in molluscs Authors: Panagiotidis, Konstantinos Abstract: Molluscs, integral to ecosystems as habitat engineers and food sources, are extremely sensitive to environmental pollution. While these animals can serve as early indicators for endocrine-disrupting chemicals (EDCs), current testing guidelines lack mechanistic underpinning due to our poor understanding of molluscan endocrinology. Previous molecular investigations have demonstrated that molluscan genomes lack essential enzymes and nuclear steroid receptors to induce vertebrate steroidogenesis. However, some steroidogenic enzymes do appear to exist in molluscs, but their function remains unknown. These include the enzymes 5-alpha-reductases (5αR1, 5αR2) that metabolise testosterone to dihydrotestosterone in vertebrates. Previous work has shown that developmental exposure of Biomphalaria glabrata embryos to pharmaceutical 5αR disruptors (dutasteride or finasteride) causes a highly reproducible and dose-dependent disruption to development, resulting in altered shell morphology. However, the impact of dutasteride on adult B. glabrata remains unexplored. This doctoral thesis aimed to fill significant knowledge gaps relating to endocrinological pathways in molluscs, investigate the expression of 5αR genes in the embryonic B. glabrata and evaluate the effects of dutasteride disruption on B. glabrata adults. Using the systematic review guidelines PRISMA, data on the occurrence of hormones, hormone receptors and hormone-metabolising enzymes in Mollusca was identified from 145 eligible studies (published between 2012-2021) and was systematically collected, evaluated and visualised in an openly accessible interactive database. By developing a RT-qPCR assay and validating stable reference genes across embryonic stages of B. glabrata, the transcript expression of genes encoding 5αR1 and 5αR2 was assessed. Lastly, the effects of dutasteride on B. glabrata adults were evaluated using a 21-day flow-through exposure and an OECD 243 static-renewal test, both with nominal exposure concentrations of 0, solvent control, 1 μg/L, 3.2 μg/L, 10 μg/L, 32 μg/L and 100 μg/L dutasteride. The systematic investigations revealed that most studies assessed were found to be heavily skewed towards vertebrate-type sex steroidogenesis, with over 62% measuring 17β-estradiol in mollusc tissues, despite unconvincing evidence that molluscs can biosynthesise vertebrate-type steroids. However, a limited number of studies are now looking beyond vertebrate-type sex steroids and diverting their focus towards the role of thyroid hormones, phytosterols (plant sterols) and ecdysteroids (insect steroids) in molluscs. The results of the RT-qPCR experiments suggest that 5αR1 and 5αR2 genes are not differentially expressed across day 2 - day 4 post-oviposition embryonic stages. Whereas the minimal variation of the five candidate reference genes UBI, TUB, EF1a, ACTIN-1, and H2A across day 2 - day 5 post-oviposition stages, makes them reliable models for normalising gene expression in embryonic B. glabrata. Importantly, under static-renewal conditions, dutasteride was observed to cause unexpected mortalities and significant declines in reproductive output of adults at concentrations above 3.2 μg/L and 32 μg/L, respectively. Together, the findings of this thesis provide novel insights into underexplored endocrinological pathways in molluscs that could be targets of endocrine disruption. Moreover, novel findings on the expression of 5αR in embryonic B. glabrata and data on the reproductive toxicity of dutasteride may help enhance our understanding of the role of 5αR in this species. Description: This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University London

From riverbank to the sea: An initial assessment of plastic pollution along the Ciliwung River, Indonesia

2024-10-23T02:01:13Z

Title: From riverbank to the sea: An initial assessment of plastic pollution along the Ciliwung River, Indonesia Authors: Cordova, MR; Kelly, MR; Hafizt, M; Wibowo, SPA; Ulumuddin, YI; Purbonegoro, T; Yogaswara, D; Kaisupy, MT; Subandi, R; Sani, SY; Thompson, RC; Jobling, S Abstract: This study presents the first comprehensive analysis of anthropogenic debris on the riverbanks of the Ciliwung River, covering upstream to downstream areas. The mean of debris found in each measurement was 32.79 ± 15.38 items/m2 with a weight of 106.00 ± 50.23 g/m2. Plastic debris accounted for over 50 % of all litter items identified and represents 55 % by weight, signifying a significantly high prevalence compared to global studies examining litter along riverbanks. The majority of the plastics found originated from Single-use applications and were predominantly made from Styrofoam. This investigation demonstrated the importance of actions to reduce single use applications and to improve waste management strategies. This can be achieved through proactive initiatives coupled with adaptable approaches, such as implementing effective urban planning and enhancing waste collection capacity. Description: Data availability: Data will be made available on request.; Supplementary data are available online at: https://www.sciencedirect.com/science/article/pii/S0025326X24006398?via%3Dihub#s0090 .