Toxicology Centre

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Valley fever under a changing climate in the United States
(Elsevier, 2024-10-11) Howard, Madelynn; Sayes, Christie; Giesy, John; Li, Yang
This review summarizes studies on the relationships between climate change and Valley Fever (VF), also termed Coccidioidomycosis, a potentially fatal upper-respiratory fungal infection caused by the pathogenic fungi, C. immitis or C. posadasii. The intensified onset of climate change has caused frequencies and possibly intensities of natural hazard events like dust storms and drought to increase, which has been correlated with greater prevalence of VF. These events, followed by changes in patterns of precipitation, not only pick up dust and spread it throughout the air, but also boost the growth and spread of Coccidioides. In California alone, cases of VF have increased fivefold from 2001 to 2021, and are expected to continue to increase. From 1999 to 2019, there was an average of 200 deaths per year caused by VF in the United States. The number of deaths caused by VF fluctuates year to year, but because more infections are predicted to occur due to a changing climate, deaths are expected to rise; thus, the rising prevalence of the disease is becoming a larger focus of the scientific community and poses an increased threat to public health. By reviewing recent and past studies on Coccidioidomycosis and its relationships with climate factors, we categorize future impacts of this disease on the United States, and highlight areas that need more study. Factors affecting the incidence of VF, such as modes of dispersal and the optimum environment for Coccidioides growth, that could potentially increase its prevalence as weather patterns change are discussed and how the endemic regions could be affected are assessed. In general, regions of the United States, including California and Arizona, where VF is endemic, are expanding and incidences of VF are increasing in those areas. The surrounding southern states, including Nevada, New Mexico, Utah, and Texas, are experiencing similar changes. In addition, the entire endemic region of the United States is predicted to spread northward as drought is prolonged and temperatures steadily increase. The findings from the keyword search from eight databases indicate that more studies on VF and its relation to dust and climate are needed especially for endemic states like Nevada that are currently not adequately studied. Overall, results of this survey summarize mechanisms and climate factors that might drive spread of VF and describes trends of incidence of VF in endemic states and predicted likely trends that might occur under a changing climate. Through reviewing recent and past studies of Coccidioidomycosis and its relationships with climate factors, future impacts of this disease have been categorized and speculated on effects it might have on the United States. Better understanding of how climate factors affect VF as well as identifying regions that require more research could inform both environmental managers and medical professionals with the resources needed to make more accurate predictions, design better mitigation strategies, send timely warnings, and protect public health.
Chronic radium-226 bioaccumulation and toxicity in the aquatic invertebrate Daphnia magna
(Springer, 2025-01-06) Lacroix-Durand, Charlotte; Janz, David; Liber, Karsten
Mining operations in Canada, including uranium mining and milling, generate by-products containing radionuclides, including radium-226 (226Ra), a long-lived, bioaccumulative calcium (Ca2+) analog. Despite strict discharge regulations, there is limited evidence to suggest that current thresholds for 226Ra adequately protect aquatic organisms. Furthermore, Canada lacks a federal water quality guideline for 226Ra, underscoring the need for protective limits to safeguard aquatic ecosystems. Hence, this research aimed to generate data on 226Ra toxicity to the model aquatic invertebrate Daphnia magna. For this purpose, two 21-day chronic toxicity tests with D. magna were conducted, with survival and reproduction as the endpoints, as well as a reduced water hardness experiment, a multigenerational study, and a bioaccumulation assay. These experiments demonstrated that a high activity concentration (nominal 50 Bq/L) of 226Ra can significantly impact the survival of D. magna. 226Ra was also found to bioaccumulate in D. magna with a BAF of 72.8. Since the Canadian Metal and Diamond Mining Effluent Regulations (MDMER) monthly mean effluent limit is currently set at 0.37 Bq 226Ra /L, the limit for composite samples at 0.74 Bq/L 226Ra, and the limit for grab samples at 1.11 Bq/L 226Ra, it is unlikely that toxic effects to aquatic cladocerans like D. magna from 226Ra will be observed downstream of Canadian mines and mills.
Chronic Radium-226 Toxicity to and Oxidative Stress in the Aquatic Invertebrate Chironomus dilutus
(Oxford University Press, 2025-01-12) Lacroix-Durand, Charlotte; Janz, David; Liber, Karsten
The mining industry, including uranium mining and milling, is of high importance in Canada. It is, however, important to consider that ore processing can result in the creation of by-products that contain radionuclides such as radium-226 (226Ra). Even with the strict discharge regulations in place, there is limited evidence to suggest that the current Canadian regulatory thresholds for 226Ra are protective for aquatic life. This concern underscores the importance of generating toxicity data for 226Ra, as no federal Canadian water quality guidelines for 226Ra currently exist to safeguard aquatic ecosystems. The potential ecological risks of 226Ra are significant due to its high mobility under typical environmental conditions, long half-life (t1/2 ~ 1,600 years), bioaccumulative properties, and similarity to calcium (Ca2+). Considering this, the primary objective of this research was to gather data on the toxicity of 226Ra to the aquatic invertebrate Chironomus dilutus. For this purpose, a partial life cycle experiment was conducted, with larval growth, survival and pupation, and emergence and sex ratio of emerged adults, as the experimental endpoints. In addition, an assessment of oxidative stress as a potential cause of toxicity was performed. These experiments revealed that elevated activity concentrations of 226Ra (25.5 Bq/L) can significantly impact the growth of C. dilutus. However, none of the other nonlethal endpoints were significantly affected by 226Ra exposure, and there was no evidence of oxidative stress in exposed C. dilutus. Finally, 226Ra was shown to adsorb onto the silica sand used as a substrate for all experiments and desorbed following acid extraction.
Selenium toxicity in fishes: A current perspective
(Chemosphere, 2024-09) Uddin, Md Helal; Ritu, Jinnath Rehana; Putnala, Sravan Kumar; Rachamalla, Mahesh; Chivers, Douglas P; Niyogi, Som
Anthropogenic activities have led to increased levels of contaminants that pose significant threats to aquatic organisms, particularly fishes. One such contaminant is Selenium (Se), a metalloid which is released by various industrial activities including mining and fossil fuel combustion. Selenium is crucial for various physiological functions, however it can bioaccumulate and become toxic at elevated concentrations. Given that fishes are key predators in aquatic ecosystems and a major protein source for humans, Se accumulation raises considerable ecological and food safety concerns. Selenium induces toxicity at the cellular level by disrupting the balance between reactive oxygen species (ROS) production and antioxidant capacity leading to oxidative damage. Chronic exposure to elevated Se impairs a wide range of critical physiological functions including metabolism, growth and reproduction. Selenium is also a potent teratogen and induces various types of adverse developmental effects in fishes, mainly due to its maternal transfer to the eggs. Moreover, that can persist across generations. Furthermore, Se-induced oxidative stress in the brain is a major driver of its neurotoxicity, which leads to impairment of several ecologically important behaviours in fishes including cognition and memory functions, social preference and interactions, and anxiety response. Our review provides an up-to-date and in-depth analysis of the various adverse physiological effects of Se in fishes, while identifying knowledge gaps that need to be addressed in future research for greater insights into the impact of Se in aquatic ecosystems.
A review of the neurobehavioural, physiological, and reproductive toxicity of microplastics in fishes
(Ecotoxicology and Environmental Safety, 2024-09) Hasan, AKM Munzurul; Hamed, Mohamed; Hasan, Jabed; Martyniuk, Christopher J.; Niyogi, Som; Chivers, Douglas P.
Microplastics (MPs) have emerged as widespread environmental pollutants, causing significant threats to aquatic ecosystems and organisms. This review examines the toxic effects of MPs on fishes, with a focus on neurobehavioural, physiological, and reproductive impacts, as well as the underlying mechanisms of toxicity. Evidence indicates that MPs induce a range of neurobehavioural abnormalities in fishes, affecting social interactions and cognitive functions. Altered neurotransmitter levels are identified as a key mechanism driving behavioural alterations following MP exposure. Physiological abnormalities in fishes exposed to MPs are also reported, including neurotoxicity, immunotoxicity, and oxidative stress. These physiological disruptions can compromise the individual health of aquatic organisms. Furthermore, reproductive abnormalities linked to MP exposure are discussed, with a particular emphasis on disruptions in endocrine signaling pathways. These disruptions can impair reproductive success in fish species, impacting population numbers. Here we explore the critical role of endocrine disruptions in mediating reproductive effects after exposure to MPs, focusing primarily on the hypothalamic-pituitary-gonadal axis. Our review highlights the urgent need for interdisciplinary research efforts aimed at elucidating the full extent of MP toxicity and its implications for aquatic ecosystems. Lastly, we identify knowledge gaps for future research, including investigations into the transgenerational impacts, if any, of MP exposure and quantifying synergetic/antagonistic effects of MPs with other environmental pollutants. This expanded knowledge regarding the potential risks of MPs to aquatic wildlife is expected to aid policymakers in developing mitigation strategies to protect aquatic species.
Molecular docking and in silico analysis of the pharmacokinetics, toxicological profile and differential gene expression of bioactive compounds from Cyrtopodium glutiniferum
(Toxicology Reports, 2024-11) Araujo, Natalia Gonçalves Ribeiro; Carlos da Silva Junior, Francisco ; Santos, Lizandra; Batistuzzo de Medeiros, Silvia; Felzenszwalb, Israel; Araujo Lima, Carlos Fernando
The genus Cyrtopodium, from the Orchidaceae family, is widely used for its therapeutic properties in the treatment of tuberculosis, abscesses, urinary infection, and colds. C. glutiniferum, one of the species of this genus, is endemic in Brazil and largely used in herbal medicine. Thus, it is of great interest to recognize its composition, the properties of the molecules found in it. This study aimed to perform the in silico analysis of the main compounds from C. glutiniferum, on the platforms pKCSM, SwissADME, LAZAR, CLC-pred, ToxTree, DIGEPred, STRING, and Cytoscape. Further than this, the molecular docking was performed. The compounds present in the aqueous extract of C. glutiniferum were identified by UHPLC-MS/MS, finding Arbutin, Caffeic acid 4-O-glucoside, and Dihydroformononetin as the three most abundant molecules. The evaluation of the gastrointestinal absorption of Dihydroformononetin is given as high, also managing to cross the blood-brain barrier, while Arbutin can only be absorbed by the gastrointestinal tract and Caffeic acid 4-O-glucoside had very low absorption. Further analysis showed that Arbutin and Dihydroformononetin are possible leading molecules for drug synthesis, according to the prediction. Toxicological aspects were analysed, and no adverse effects were noted, but there were divergences in the mutagenic prediction of Arbutin and Dihydroformononetin, having different results in the used platforms, demonstrating that a cautious analysis and data insertion is needed in these tools to optimize them. The analysis of the differentially expressed genes predicted that the compounds can regulate several genes, including some genes associated with carcinogenesis and inflammation. The Molecular docking analysis showed high binding affinities of the molecules with different proteins. Therefore, C. glutiniferum demonstrates the potential to be used as a phytotherapeutic. The same was given through the in silico analysis of the three compounds found in the orchid, that show good individual potential.
Unveiling the molecular effects of replacement and legacy PFASs: Transcriptomic analysis of zebrafish embryos reveals surprising similarities and potencies.
(American Chemical Society, 2024-10-11) Mahoney, Hannah; Ankley, Phillip; Roberts, Catherine; Lamb, Alicia; Schultz, Matthew; Zhou, Yutong; Giesy, John; Brinkmann, Markus
The prevalence of per- and poly fluoroalkyl substances (PFASs) in the environment has prompted restrictions on legacy PFASs due to their recognized toxic effects. Consequently, alternative “replacement” PFASs have been introduced and are prevalent in environmental matrices. Few studies have investigated the molecular effects of both legacy and replacement PFASs under short-term exposures. This study aimed to address this by utilizing transcriptomic sequencing to compare the molecular impacts of exposure to concentrations 0.001–5 mg/L of the legacy PFOS and two of its replacements, PFECHS and FBSA. Using zebrafish embryos, the research assessed apical effects (mortality, morphology, and growth), identified differentially expressed genes (DEGs) and enriched pathways, and determined transcriptomic points of departure (tPoDs) for each compound. Results indicated that PFOS exhibited the highest relative potency, followed by PFECHS and then FBSA. While similarities were observed among the ranked DEGs across all compounds, over-representation analysis revealed slight differences. Notably, PFOS demonstrated the lowest tPoD identified to date. These findings raise concerns regarding the safety of emerging replacement PFASs and challenge assumptions about PFAS toxicity solely resulting from their accumulative potential. As replacement PFASs proliferate in the environment, this study underscores the need for heightened scrutiny of their effects and questions current regulatory thresholds.
Continental-scale nutrient and contaminant delivery by Pacific salmon
(Nature, 2024-10-09) Brandt, Jessica E.; Wesner, Jeff F.; Ruggerone, Gregory; Jardine, Timothy D; Eagles-Smith, Collin A.; Ruso, Gabrielle E.; Stricker, Craig A.; Voss, Kristofor A.; Walters, David M.
The movement of large amounts of nutrients by migrating animals has ecological benefits for recipient food webs that may be offset by co-transported contaminants. Salmon spawning migrations are archetypal of this process, carrying marine-derived materials to inland ecosystems where they stimulate local productivity but also enhance contaminant exposure. Pacific salmon abundance and biomass are higher now than in the last century, reflecting substantial shifts in community structure8 that probably altered nutrient versus contaminant delivery. Here we combined nutrient and contaminant concentrations with 40 years of annual Pacific salmon returns to quantify how changes in community structure influenced marine to freshwater inputs to western North America. Salmon transported tonnes of nutrients and kilograms of contaminants to freshwaters annually. Higher salmon returns (1976–2015) increased salmon-derived nutrient and contaminant inputs by 30% and 20%, respectively. These increases were dominated by pink salmon, which are short-lived, feed lower in marine food webs than other salmon species, and had the highest nutrient-to-contaminant ratios. As a result, the delivery of nutrients increased at a greater rate than the delivery of contaminants, and salmon inputs became more ecologically beneficial over time. Even still, contaminant loadings may represent exposure concerns for some salmon predators. The Pacific salmon example demonstrates how long-term environmental changes interact with nutrient and contaminant movement across large spatial scales and provides a model for exploring similar patterns with other migratory species.
Assessment of Rapid and Conventional RT-qPCR-Based Systems for Wastewater Surveillance
(ACS Publications, 2024-09-05) Asadi, Mohsen; Hamilton, Daniel; Shomachuk, Corwyn; Oloye, Femi F.; De Lange, Chantel; Liang, Jiaqi; Xia, Pu; Osunla, Charles A.; Cantin, Jenna; Mejia, Edgard M.; Gregorchuk, Branden S. J.; Becker, Michael G.; Mangat, Chand; Brinkmann, Markus; Jones, Paul D.; Giesy, John P.; McPhedran, Kerry M.
Conventional wastewater surveillance (WS) relies on highly trained personnel, advanced instrumentation, and significant resources, making the development and use of simple, rapid, and sensitive alternative technologies valuable for reducing costs, time, and labor intensity. For the first time, this study investigated the use of two well-developed rapid systems, including the GeneXpert and LuminUltra, in parallel with a conventional WS reference methodology for the assessment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in three cities: Saskatoon, Prince Albert, and North Battleford, Saskatchewan, Canada. RNA extractions from wastewater samples were carried out for the conventional reference and LuminUltra methods, while GeneXpert was used for both raw and concentrated wastewater samples. Bland–Altman plots showed a combination of systematic bias and random error between these real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR)-based systems. Additionally, results indicated the reasonable performance of GeneXpert in viral detection with a sensitivity rate of >98%, as compared to the conventional reference methodology of 100% and LuminUltra with >65%. A Spearman correlation test showed meaningful relationships between the GeneXpert and conventional reference methodology viral level results across all cities, indicating GeneXpert’s reliability for accurate viral detection and disease prevalence determination, specifically in limited-resource communities, with a shorter processing time and cost-effectiveness in analysis.

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