Toxicology Commons^™

Comparing Effects Of Atrazine Exposure On Neuroendocrine Molecular Targets At Two Developmental Exposure Periods In The Zebrafish, Jenna Swihart

The Journal of Purdue Undergraduate Research

No abstract provided.

The E-Liquid Flavorings Cinnamaldehyde, Vanillin, And Ethyl Vanillin Induce Cellular Stress Responses In Human Proximal Tubule (Hk-2) Epithelial Cells, Ashley J. Cox

Theses, Dissertations and Capstones

The use of electronic nicotine delivery systems (ENDS) has become popular in recent years as an alternative to traditional cigarettes. These devices heat and subsequently vaporize e-liquids for inhalation by the user, which allows for the delivery of ingredients such as flavorings, nicotine, and solvents through the vapor. Flavorings used in e-liquids are “generally recognized as safe” (GRAS) for consumption by the Food and Drug Administration (FDA), however there are currently no recommendations on safety regarding the inhalation of flavoring agents. While research characterizing effects of e-liquids and their flavorings is abundant in lung and respiratory tract models, few studies …

Pharmacokinetic Modeling Of Metonitazene And Isotonitazene Using In Vitro And In Vivo Models And Comparison To Human Postmortem Casework, Justine P. Sorrentino

Theses and Dissertations

Metonitazene and isotonitazene are two benzimidazole opioids that are contributing to the opioid crisis nationwide. Limited pharmacokinetic data has been published on these nitazene compounds, therefore this study sought to determine if these two structurally similar opioids would have comparable half-lives and clearance utilizing in vitro and in vivo models. Using the data determined in the pharmacokinetic study, and by testing human postmortem cases, this study aimed to inform interpretation of these drugs detected in human casework. Sample analysis for all aspects of the study was performed utilizing LC/MS/MS. In vitro pharmacokinetics of both drugs were examined using a human …

Streptozotocin-Induced Diabetes Increases Kidney Toxicity In Rats Exposed To Ochratoxin A, Belkys Gonzalez

Theses and Dissertations

Due to the rising occurrence of diabetes in the population and the prevalence of OTA exposure via ingestion of contaminated foodstuffs, there is a need to assess the possible renal interaction of a diabetic disease state in concurrence with OTA exposure. Sprague Dawley rats were treated with streptozotocin to induce experimental diabetes and then orally exposed to 0.5 mg/kg body weight OTA once a day for 21 days. Renal biomarkers and light microscopy were evaluated to assess the interaction between diabetic nephropathy and OTA exposure. LLC-PK1 proximal tubule cells were used as an in vitro model to assess the potential …

Exposure To Dithiocarbamate Fungicide Ziram Results In Hepatic And Renal Toxicity In Long-Evan Rats, Jeffrey Chen

Theses and Dissertations

Ziram is a broad spectrum fungicide that is used on a variety of crops. It has been shown to display a wide array of toxicological effects, however, there is still a scarcity of mechanistic data regarding how it facilitates those effects. One of its presumed mechanisms of toxicity is due to the production of oxidative stress. However, whether the production of oxidative stress is due to its dimethyldithiocarbamate backbone, its metal moiety, or a combination of both, is still unknown. Contributing to the production of oxidative stress is ziram’s ability to alter essential metal homeostasis through transchelation of other essential …

Determination Of Genetic Variation In Opioid-Resistant Hospice Patients Using A Pharmacogenomics Approach, Daniel Bianculli

Theses and Dissertations

Managing pain requires a delicate balance between the advantages of opioid analgesia and the possible adverse effects. This balance becomes even more difficult in hospice and palliative care environments where dosage regimens are frequently ambiguous. Some hospice patients experience opioid resistance, in which opioids no longer produce an analgesic effect on a patient. Evidence-based analyses frequently omit this vulnerable population, resulting in a need for concrete procedures. The emergence of pharmacogenomic analysis and personalized treatment presents a solution to this problem by using each patient's genomic data to interpret opiate dosing. This pharmacogenomic study aimed to single nucleotide polymorphisms (SNPs) …

Evaluation Of Microglia’S Structural Variations Within An Organotypic Hippocampal Slice Model After Regionalized Toxic Injury, Jesus Antonio Trejos

Theses and Dissertations

The dendritic cells of the CNS, the microglia (MG), are an initiation point of the immunological response within the post blood-brain barrier (BBB) compartment. Microglia morphology drastically changes in response to cell stress to a much different non-dendritic morphology. This investigation postulates that if the first MG responses to toxic injury are isolated and studied in greater morphological detail there is much to be learned about MG metamorphosis from a baseline (M2) to an activated (M1) state. The organotypic hippocampal slice was the experimental setting used to investigate microglial response to toxic injury. This isolates dendritic cellular responses and associated …

Combined Cytotoxicity Of The Herbicide Glyphosate And The Fungicide Mancozeb In Mouse Neuroblastoma Cells, Heidi Ebid

Theses and Dissertations

The herbicide glyphosate and the fungicide mancozeb are globally applied on a variety of agricultural crops. Residues of both pesticides are frequently detected in food and water. Combined exposure to both compounds is therefore possible. Glyphosate and mancozeb have been separately investigated in previous studies and were shown to induce neurotoxicity. The current study investigates the cytotoxicity of different glyphosate and mancozeb combinations including mixture of mancozeb + glyphosate, combination of mancozeb followed by glyphosate and combination of glyphosate followed by mancozeb and compares neurotoxicity seen with the combinations to that of glyphosate or mancozeb using mouse neuroblastoma Neuro-2a cells. …

Exposition Professionnelle Des Femmes Aux Substances Chimiques : Amélioration D’Une Matrice Emploi Exposition Existante Pour Fournir Des Estimations Spécifiques Au Sexe : Rapport Abrégé, Vikki Ho, Chelsea Almadin, France Labrèche, Mark Goldberg, Marie-Élise Parent, Jack Siemiatycki, Jérôme Lavoué

Rapports de recherche scientifique

Il est reconnu que les femmes et les hommes ont des profils professionnels différents qui peuvent donc se traduire par des risques de maladie professionnelle différents. Pourtant, la plupart de nos connaissances actuelles sur les maladies professionnelles découlent d'études menées auprès des hommes. Or, les femmes représentent actuellement 48 % de la population active au Québec. La santé des femmes dans l’environnement de travail demeure un domaine sous-étudié et nous sommes particulièrement freinés par le manque de compréhension de l'impact du genre sur l'exposition en milieu de travail. Il a été démontré que l'attribution des tâches et les conditions de …

Occupational Exposures Of Women To Chemical Substances: Improvement Of An Existing Job Exposure Matrix To Provide Sex-Specific Estimations Of Exposure, Vikki Ho, Chelsea Almadin, France Labrèche, Mark Goldberg, Marie-Élise Parent, Jack Siemiatycki, Jérôme Lavoué

Rapports de recherche scientifique

Il est reconnu que les femmes et les hommes ont des profils professionnels différents qui peuvent donc se traduire par des risques de maladie professionnelle différents. Pourtant, la plupart de nos connaissances actuelles sur les maladies professionnelles découlent d'études menées auprès des hommes. Or, les femmes représentent actuellement 48 % de la population active au Québec. La santé des femmes dans l’environnement de travail demeure un domaine sous-étudié et nous sommes particulièrement freinés par le manque de compréhension de l'impact du genre sur l'exposition en milieu de travail. Il a été démontré que l'attribution des tâches et les conditions de …

Investigating The Impact Of Chronic Inflammatory Pain On Ethanol Consumption In Mouse Models., Joshua L. Hunt

Theses and Dissertations

Chronic pain affects nearly 20% of Americans annually and for many alcohol provides a convenient and legally acquired palliative. Population-based studies have suggested a link between increased alcohol use and reduced pain, but chronic or excessive alcohol use potentiates the risk to develop alcohol dependence and neuropathy. However, sex differences in chronic pain and alcohol abuse are still not well understood. In the present study, we investigated whether chronic inflammatory pain using the inflammatory agent Complete Freund’s Adjuvant (CFA) model could alter ethanol consumption in male and female C57BL/6J mice. We observed that only CFA-treated male mice increased their ethanol …

The Effects Of Alcohol On Crash Avoidance Reaction Time In A Driving Simulator Task In Humans, Aishwarya Vasudevan

Wayne State University Theses

AIM 1: Alcohol-impaired driving continues to be a significant cause of car crash injuries and deaths. The blood alcohol concentration (BAC) cut-off level for drunk driving is 0.08% in Michigan, and is estimated that lowering this cut-off to 0.05%would save 500–800 lives every year in the US alone. We used a portable virtual reality (VR)-based driving simulator to demonstrate the effects of alcohol at BAC concentrations 0.02-0.08%, grouped into 0.01% increments, on driving performance, specifically Crash Avoidance Reaction Time (CART), i.e., the time (in msec) required to initiate a steering avoidance response. We found that BAC concentrations as low as …

Lead Bioaccessibility And Commonly Measured Soil Characteristics (Detroit, Mi, Usa) – Phase 1, Sabrina R. Good, Allison R. Harris, Patrick Crouch, Conor T. Gowan, William D. Shuster, Shawn P. Mcelmurry

Open Data at Wayne State

Contaminated urban soil is one of the major contributors to child Pb exposure. To gain a better understanding of Pb risk in urban areas, composite samples were collected from 142 residential, privately owned, parcels in Detroit, Hamtramck, and Highland Park, Michigan, with approval from the property owners. The proximity of soil sampling and former smelter locations were also reported. Sample were collected from areas covered with turf grass. Four samples were collected, one from each cardinal direction (north, south, east, and west), 20 cm from an aluminum tent stake driven into the center of the sampling site. Soils were collected …

Exploring Serotonin 1b Autoreceptor Mediated Regulation Of Serotonin Transporter In Female Mice, Sanyukta Jalihalkar

Theses and Dissertations

Rationale: Serotonin (5-HT) is a crucial neurotransmitter involved in regulating various physiological processes. Dysregulation of the serotonergic system has been implicated in several neuropsychiatric disorders. Though numerous 5-HT receptors exist, the 5-HT transporter (SERT) is responsible for 5-HT clearance in the brain and periphery. 5-HT_1Bautoreceptors regulate 5-HT release and interact with glycogen synthase kinase-3β (GSK3β), which can modulate SERT function via specific Ser44/48 phosphorylation sites. While these findings suggest a potential interplay between 5-HT_1Band GSK3β-mediated SERT phosphorylation in regulating extracellular 5-HT, the primary causal molecular link remains unknown.

Objectives: To investigate if 5-HT_1B activation by …

A Review Of Rattlesnake Venoms, Phuc Phan, Anant Deshwal, Tyler Anthony Mcmahon, Matthew Slikas, Elodie Andrews, Brian Becker, Thallapuranam Krishnaswamy Suresh Kumar

Chemistry & Biochemistry Faculty Publications and Presentations

Venom components are invaluable in biomedical research owing to their specificity and potency. Many of these components exist in two genera of rattlesnakes, Crotalus and Sistrurus, with high toxicity and proteolytic activity variation. This review focuses on venom components within rattlesnakes, and offers a comparison and itemized list of factors dictating venom composition, as well as presenting their known characteristics, activities, and significant applications in biosciences. There are 64 families and subfamilies of proteins present in Crotalus and Sistrurus venom. Snake venom serine proteases (SVSP), snake venom metalloproteases (SVMP), and phospholipases A2 (PLA2) are the standard components in Crotalus …

Geochemistry Of Rare Earth Elements In Simulated Natural Waters: Experiments And Modelling Of Precipitation, Complexation, And Bioavailability., Samantha Zulian

Theses and Dissertations (Comprehensive)

Rare earth elements (REEs) are an important part of modern technology and used for many applications. Mining, agriculture, improper recycling and medical applications can increase the concentration of these elements in surface waters. Metals in the environment including REEs can be found naturally but understanding the implications increase concentrations from anthropogenic inputs is important. REE mobility, persistence and toxicity is imperative to risk assessment as Canada begins to mine REE. Ultimately, as with other metals, the impacts of REEs in the environment should be dependent on the specific physical and chemical forms of the elements. Fractionation provides a practical method …

Evaluating The Risk Posed By Gadolinium In The Grand River Watershed, Johann Memmel

Theses and Dissertations (Comprehensive)

Gadolinium (Gd) is a rare earth element (REE), primarily used in contrast agents for magnetic resonance imaging (MRI), with additional applications in metallurgy, phosphors, neutron shielding, and other niche applications. Both Gd and Gd-based contrast agents (GBCAs, the form used for MRIs) have been detected downstream of wastewater effluent discharges and there is currently little research into the risk this poses to aquatic ecosystems. This study investigated the potential environmental risks of Gd and GBCAs using the Grand River watershed (GRW) in southwestern Ontario as a model ecosystem due to it containing a variety of land uses (urban, industrial, agricultural) …

Assessing Stormwater Management Pond Water Quality, Function, And The Potential Biotic Effects To Receiving Waters, Mitchell Elstone

Theses and Dissertations (Comprehensive)

The use of stormwater management ponds (SWMPs) has been increasing over the past five decades. However, an in-depth understanding of the daily performance of SWMPs and functionality during cold periods is limited. This is in part because mandated monitoring is relatively infrequent, and the assumption that SWMPs are inactive between storm events and during the winter. The goals of this research were to better understand daily stormwater (SW) characteristics, the performance of SWMPs based on current forms of evaluation and assess the potential for SWMP effluent to impact downstream biota. Influent and effluent samples from two SWMPs were collected daily …

Exploring The Dual Role Of Vegf165 In Bleomycin Induced Lung Injury And Recovery In A Aav Mice Model, Igor Ban

Theses and Dissertations

Pulmonary fibrosis (PF) poses a significant challenge in respiratory medicine due to its complex etiology and progression characterized by excessive lung scarring, leading to compromised pulmonary function. The multifaceted roles of Vascular Endothelial Growth Factor A (VEGF-A) and specifically its isoform VEGF-A165 are critical in this context, given their involvement in angiogenesis, lymphangiogenesis, and tissue repair. The dual nature of VEGF-A165, promoting angiogenesis and potentially exacerbating or mitigating fibrosis, underscores its significance in both the progression and recovery phases of PF. Our work, explores the nuanced functions of VEGF-A165 using AAV1 as a gene delivery vector to overexpress this growth …

The Effects Of Length, Weight, Age, And Gender On Mercury Concentrations In Burbot In North-Central Minnesota Lakes, Liam Hanley

Journal of Earth and Life Science

Burbot Lota lota in north-central Minnesota lakes have the potential to reach large sizes and consume large volumes of prey. This caveat may make burbot susceptible to higher rates of biocontamination, bioaccumulation and biomagnification. The objective of this study was to determine how changes in age, length, gender, weight, and lake affect total mercury concentrations in burbot. In this experiment 28 burbot were angled from three lakes: Cass (n = 17), Winnibigoshish (n = 4), and Bad Medicine (n = 7). Then tissue samples were taken from each fish and were lyophilized and homogenized. Homogenized tissue samples were analyzed by …

Observed Effects Of Physiological Melatonin Dosing On Mda-Mb-231 Breast Cancer Cell Proliferation, Wenli Wu

Williams Honors College, Honors Research Projects

This project seeks to evaluate pharmacological dosing of melatonin on the cell proliferation of MDA-MB-231 breast cancer cell line in culture, using the two solubility carriers: DMSO/water and ethanol. This experiment is a component of ongoing research at the Eaton lab which will elucidate melatonin dose-response toxicology in zebrafish and a possible breast cancer xenograft model for novel treatment therapies.

Emerging Chromatin Regulators In Response To Heavy Metal Exposure, Wesley Saintilnord

Theses and Dissertations--Molecular and Cellular Biochemistry

Environmental exposure to heavy metals poses significant threats to human health as they are associated with various developmental and chronic pathologies such as reproductive defects and cancers. Despite their profound risks, a comprehensive understanding of their disease-causing mechanisms is lacking. Most studies point to reactive oxygen species-induced DNA damage; however, their mutagenic potential is relatively weak suggesting the involvement of alternative mechanisms. One important, yet underexplored mechanism, is their ability to rewire the epigenome via DNA methylation and histone variant incorporation, leading to aberrant gene regulatory networks.

This study investigates the epigenetic mechanisms targeted by two ubiquitous heavy metals with …

Enhancing Translation: A Need To Leverage Complex Preclinical Models Of Addictive Drugs To Accelerate Substance Use Treatment Options, Christa Corley, Ashley Craig, Safiyah M. Sadek, Julie A. Marusich, Samar N. Chehimi, Ashley M. White, Lexi J. Holdiness, Benjamin C. Reiner, Cassandra D. Gipson

Markey Cancer Center Faculty Publications

Preclinical models of addictive drugs have been developed for decades to model aspects of the clinical experience in substance use disorders (SUDs). These include passive exposure as well as volitional intake models across addictive drugs and have been utilized to also measure withdrawal symptomatology and potential neuro- behavioral mechanisms underlying relapse to drug seeking or taking. There are a number of Food and Drug Administration (FDA)-approved medications for SUDs, however, many demonstrate low clinical efficacy as well as potential sex differences, and we also note gaps in the continuum of care for certain aspects of clinical ex- periences in individuals …

Perfluorooctanesulfonic Acid Exposure Leads To Downregulation Of 3-Hydroxy-3-Methylglutaryl-Coa Synthase 2 Expression And Upregulation Of Markers Associated With Intestinal Carcinogenesis In Mouse Intestinal Tissues, Josiane Weber Tessmann, Pan Deng, Jerika Durham, Chang Li, Moumita Banerjee, Qingding Wang, Ryan A. Goettl, Daheng He, Chi Wang, Eun Y. Lee, B. Mark Evers, Bernhard Hennig, Yekaterina Y. Zaytseva

Markey Cancer Center Faculty Publications

Perfluorooctanesulfonic acid (PFOS) is a widely recognized environment pollutant known for its high bio- accumulation potential and a long elimination half-life. Several studies have shown that PFOS can alter multiple biological pathways and negatively affect human health. Considering the direct exposure to the gastrointestinal (GI) tract to environmental pollutants, PFOS can potentially disrupt intestinal homeostasis. However, there is limited knowledge about the effect of PFOS exposure on normal intestinal tissues, and its contribution to GI- associated diseases remains to be determined. In this study, we examined the effect of PFOS exposure on the gene expression profile of intestinal tissues of …

Quantum Dots' Toxicity: A Multi-Level Investigation On The Impact Of Quantum Dots On The Actin Cytoskeleton, Nhi Le

Graduate Theses/Dissertations

Quantum dots (QDs) are fluorescence nanomaterials with unique optical and physical properties. As such, they are highly sought after for their potential use in several biomedical and industrial applications. Despite their vast potential, recent studies have suggested that quantum dots are toxic to cells. Yet, the mechanism of quantum dots’ toxicity remains unclear. As such, my thesis aims to comprehensively examine the mechanism of quantum dots’ toxicity, emphasizing how quantum dots disrupt the actin cytoskeleton. In this study, I used RNA sequencing and mass spectrometry to investigate the influence of CdSe/ZnS QDs on the transcriptomic proteomic level of Saccharomyces cerevisiae …

Nanotoxicology Of Cdse/Zns Quantum Dot Alternatives In Thle-2 And Hepg2 Liver Cells, Seth Harris

Graduate Theses/Dissertations

Fluorescent nanoparticles known as quantum dots (QDs) have unique properties that make them useful in biomedicine. Specifically, CdSe/ZnS QDs, while good at fluorescing, show toxicity. Due to this, safer alternatives have been developed. This study uses an XTT viability assay, ROS fluorescent imaging, and apoptosis to investigate the effect of QD alternatives InP/ZnS, CuInS₂/ZnS, and carbon dots (NCD) in liver cells. The liver is a possible destination for accumulation of QDs making it an appropriate model for testing. A cancerous liver cell line known as HepG2, and an immortalized liver cell line known as THLE-2 were used. At …

Effects Of Subchronic Oral Pfos Exposure Via Drinking Water On Gut Microbiota Composition, Emma Ann Loder

Graduate Theses/Dissertations

Perfluorooctanesulfonic acid (PFOS) has been phased out of production in the United States, but because of its resistance to degradation and its persistence in the environment, PFOS can be found in drinking water across America. Oral exposure to PFOS has been linked to adverse developmental, immunological, hepatic, and endocrine health. Oral PFOS exposure may alter the gut microbiota and cause dysbiosis, which is implicated in the pathology of inflammatory diseases like Crohn’s disease, diabetes, and ulcerative colitis. The goal of the study was to investigate the effects of subchronic oral PFOS exposure on the composition of the gut microbiota. Adult …

Neurodevelopmental Vulnerability To Gestational Ozone Exposure, Vishnupriya Alavala, Sarah E. Brent, Christopher G. Canal, Joseph Wang, Russell P. Hunter, Matthew J. Campen, Andrew K. Ottens

Undergraduate Research Posters

Ambient air pollution accounts for about 4.2 million premature deaths annually per the World Health Organization. Ozone (O3) is a highly reactive air pollutant found in smog and is implicated in cellular damage leading to organ dysfunction. Ambient air pollution is associated with neurodevelopmental, behavioral, and cognitive disorders though ozone’s role is unknown. Studies here look at ozone exposure shortly after implantation vs. shortly before term to evaluate differences in neurodevelopmental susceptibility over time.

To inquire on the effects of ozone on the fetal brain, pregnant Sprague-Dawley rats were exposed once to 0.3 ppm of O3 or filtered air (FA) …

Aversion Properties Of Retrorsine, Retrorsine Nitrogen Oxide And Frosted Senecio Latifolius, Leendert D. Snyman

Poisonous Plant Research (PPR)

Two pilot trials, investigating the aversive properties of retrorsine and retrorsine nitrogen oxide and that of frosted Senecio latifolius, were executed. Retrorsine and retrorsine-NO (the toxic principles of Senecio retrorsus), unlke sceleratine-NO (the toxic principle of another hepatotoxic pyrrolizidine alkaloid containing plant, namely S. latifolius), were not capable of establishing aversion when given to a sheep. Frosted S. latifolius given to a sheep also did not induce aversion. However, a sheep averted to S. latifolius (non-frosted) refused eating frosted S. latifolius.

Sceleratin Nitrogen Oxide As Aversive Agent In Conditioning Livestock To Avoid Senecio Latifolius, Leendert D. Snyman

Poisonous Plant Research (PPR)

Sceleratine nitrogen oxide, when administered together with a dichloromethane extract of Senecio latifolius, successfully conditioned cattle and sheep to avoid milled freeze dried S. latifolius mixed with maize meal. This treatment was effectively applied in conditioning steers to refuse eating S. latifolius grown in pots.