Toxicology Commons^™

An Open-Sourced Statistical Application For Identifying Complex Toxicological Interactions Of Environmental Pollutants, Jordan T. Perkins, Michael C. Petriello, Li Xu, Arnold J. Stromberg, Bernhard Hennig

Superfund Research Center Faculty Publications

The rising number of chemicals that humans are exposed to on a daily basis, as well as advances in biomonitoring and detection technologies have highlighted the diversity of individual exposure profiles (complex body burdens). To address this, the toxicological sciences have begun to shift away from examining toxic agents or stressors individually to focusing on more complex models with multiple agents or stressors present. Literature on interactions between chemicals is fairly limited in comparison with dose-response studies on individual toxicants, which is largely due to experimental and statistical challenges. Experimental designs capable of identifying these complex interactions are often avoided …

Mechanisms Of Thymic Toxicity Induced By Environmentally Relevant Concentrations Of Arsenic, Huan Xu

Biomedical Sciences ETDs

Arsenic, a ubiquitous environmental contaminant, is known to cause immunotoxicity. However, the mechanisms of arsenic induced immunotoxicity are still not clear. Arsenite (As⁺³), the trivalent inorganic form of arsenic, was found to increase DNA damage and inhibit PARP activity in thymus cells at 50 nM in vitro. Oxidative stress and double strand breaks (DSBs) formation occurred in thymus cells exposed to As⁺³ at 500 nM. The genotoxicity was found to be related to As⁺³ exporter expressions and reversed by zinc supplement. IL-7 signaling, the critical cytokine signal for the early DN thymic T cell proliferation, …

Chloroquine-Inducible Par-4 Secretion Is Essential For Tumor Cell Apoptosis And Inhibition Of Metastasis, Ravshan Burikhanov, Nikhil Hebbar, Sunil K. Noothi, Nidhi Shukla, James Sledziona, Nathália Araujo, Meghana Kudrimoti, Qing Jun Wang, David S. Watt, Danny R. Welch, Jodi Maranchie, Akihiro Harada, Vivek M. Rangnekar

Radiation Medicine Faculty Publications

The induction of tumor suppressor proteins capable of cancer cell apoptosis represents an attractive option for the re-purposing of existing drugs. We report that the anti-malarial drug, chloroquine (CQ), is a robust inducer of Par-4 secretion from normal cells in mice and cancer patients in a clinical trial. CQ-inducible Par-4 secretion triggers paracrine apoptosis of cancer cells and also inhibits metastatic tumor growth. CQ induces Par-4 secretion via the classical secretory pathway that requires the activation of p53. Mechanistically, p53 directly induces Rab8b, a GTPase essential for vesicle transport of Par-4 to the plasma membrane prior to secretion. Our findings …

Tenofovir Induced Nephrotoxicity: A Mechanistic Study, Rachel A. Murphy

Theses, Dissertations and Capstones

Tenofovir (TFV) is a reverse transcriptase inhibitor that is approved by the United States Food and Drug Administration (FDA) to treat HIV and chronic Hepatitis B. It has a long half-life, allowing for once a day dosing and is effective in treatment of both naive and experienced patients. It is administered orally as tenofovir disoproxil fumarate (TDF) and is deesterified in plasma to the active drug TFV. However, renal impairment is associated with its use; TFV can induce decreased glomerular filtration rate (GFR) and free calcitriol, renal failure, and Fanconi Syndrome. The exact mechanism of toxicity currently remains unknown, largely …

Establishing Environmental Variability In The Toxins Produced By A Single Strain Of Prymnesium Parvum, Amy Parsons-White

Theses, Dissertations and Capstones

Prymnesium parvum (P. parvum) is a toxin producing haptophyte that has spread globally over the past 100 years. The algae, initially a marine organism, has moved inland to less saline waters. In addition, there is variability in the efficacy of the toxins produced from bloom to bloom. Variation between strains has been suggested as the reason for bloom differences; however, environmental variability within a single strain must first be established. Here, a single strain of P. parvum was cultured at three environmentally relevant salinities, 6psu, 13psu, and 35psu. Three different environmental shocks, decreased temperature, raised pH, and addition of specific …

4-Methylcyclohexanemethanol Acute Toxicity To Daphnia And Its Effects On General Esterase And Glutathione S-Transferase Activity In Fathead Minnows, Rachel Clark, Jared Lewis, Jeehoon Jung, Benjamin Thornton

Research in Biology

In 2014, 10,000 gallons of crude MCHM spilled into the Elk River in West Virginia. Due to a paucity of information about the toxicity of this chemical prior to the spill, our research aimed to verify the published 48-h EC₅₀ for Daphnia magna (Daphnia) examine the effects of MCHM on two enzyme detoxification systems, general esterase and glutathione S-transferase, in Pimephales promelas (Fathead Minnow). We used pure MCHM instead of the crude form used in Eastman’s toxicity tests because the composition of crude MCHM is variable. The EC₅₀ we obtained for pure MCHM did not differ significantly from …

Evaluation Of Childhood Exposure To Lead In Community Water Systems In Maine, Nicholas Flavin

Muskie School Capstones and Dissertations

The concentration of lead in Maine’s public drinking water was evaluated from 4,700 first-draw water samples collected from 358 Maine Community Water systems. Samples collected from 2012-2015 were obtained by request from the Maine Center for Disease Control and Prevention’s (MeCDC)’s Drinking Water Program.

Exposure and physiological uptake of lead can be mathematically modelled or predicted based on the amount of lead in “background” sources of contaminated media such as soil, dust, water, air or dietary items; the better the characterization of lead in these media, the better the exposure predictions. To assess childhood lead exposure, EPA recommends using the …

Molecularly Imprinted Polymers Synthesized As Adsorbents For Ergot Alkaloids: Characterization And In Vitro And Ex Vivo Assessment Of Effects On Ergot Alkaloid Bioavailability, Manoj B. Kudupoje

Theses and Dissertations--Animal and Food Sciences

Alkaloid toxicities negatively impact livestock health and production and are of serious economic concern to animal industries. To date, few strategies have been developed to evaluate alkaloid levels in feed or to counteract alkaloid toxicities. The present research evaluated the applicability of imprinting technology to synthesize polymers that have potential to interact with ergot alkaloids and therefore reduce their bioavailability in the GIT. The studies also evaluated applicability of synthesized polymers for use in the ruminal environment using an in vitro ruminal fermentation model, and for the ability to ameliorate vasoconstriction using ex vivo myographic evaluations.

In the first experiment, …

Knockout Of Sphingosine Kinase 1 Attenuates Renal Interstitial Fibrosis In Unilateral Ureteral Obstruction (Uuo) Model, Xiwen Zhang

Theses and Dissertations

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite and an important signaling molecule that plays a significant role in fibrosis. S1P synthesis is catalyzed by sphingosine kinases (SphKs), which phosphorylate sphingosine into S1P. The present study tested the hypothesis that SphK1-S1P signaling pathway participates in the kidney damage in unilateral ureteral obstruction (UUO) model. Wild type and SphK1 knockout mice were subjected to UUO for 7 days or 14 days and then four groups of kidneys were collected: wild type control group (WT-C), wild type UUO group (WT-UUO), SphK1-/- control group (KO-C) and SphK1-/- UUO group (KO-UUO). The mRNA level of …

The Effects Of The Hiv-1 Tat Protein And Morphine On The Structure And Function Of The Hippocampal Ca1 Subfield, William D. Marks

Theses and Dissertations

HIV is capable of causing a set of neurological diseases collectively termed the HIV Associated Neurocognitive Disorders (HAND). Worsening pathology is observed in HIV+ individuals who use opioid drugs. Memory problems are often observed in HAND, implicating HIV pathology in the hippocampus, and are also known to be exacerbated by morphine use. HIV-1 Tat was demonstrated to reduce spatial memory performance in multiple tasks, and individual subsets of CA1 interneurons were found to be selectively vulnerable to the effects of Tat, notably nNOS+/NPY- interneurons of the pyramidal layer and stratum radiatum, PV+ neurons of the pyramidal layer, and SST+ neurons …

Aluminum And Phthalates In Calcium Gluconate: Contribution From Glass And Plastic Packaging, Robert A. Yokel, Jason M. Unrine

Pharmaceutical Sciences Faculty Publications

Introduction: Aluminum contamination of parenteral nutrition solutions has been documented for three decades. It can result in elevated blood, bone, and whole body aluminum levels associated with neurotoxicity, reduced bone mass and mineral content, and perhaps hepatotoxicity. The primary aluminum source among parenteral nutrition components is glass-packaged calcium gluconate, in which aluminum concentration the past three decades has averaged~ 4000 [mu]g/L, compared to < 200 [mu]g/L in plastic container-packaged calcium gluconate. A concern about plastic packaging is leaching of plasticizers, including phthalates, which have the potential to cause endocrine (male reproductive system) disruption and neurotoxicity.

Methods: Aluminum was quantified in samples collected periodically over more than two years from three calcium gluconate sources used to prepare parenteral nutrition solutions; two packaged in glass (from France and the US) and one in plastic …

Chronic Effects Of Lead Exposure On Atherinops Affinis (Topsmelt): Influence Of Salinity And Organism Age, Erik Joseph Reynolds

Master's Theses

Pb (lead) appears in the environment as a consequence of both natural and anthropogenic processes. Mining, smelting, coal burning, lead acid batteries, and cement manufacturing substantially release Pb into aquatic environments. The goal of this study was to determine the influence of salinity and organism age on chronic toxicity of Pb to Atherinops affinis (topsmelt) in support of development of a species sensitivity distribution (SSD). Species sensitivity distributions assist in ecological risk assessments and establishing quality criteria for contaminants. Three chronic exposure studies were conducted for 28 days in a water flow-through testing system. Survival, standard length, dry weight, and …

Organ-Specific Contribution Of P450 Enzymes To Bioactivation And Acute Respiratory Tract Toxicity Of Naphthalene, Nataliia Kovalchuk

Legacy Theses & Dissertations (2009 - 2024)

Naphthalene (NA) is an omnipresent air pollutant and respiratory toxicant and a possible human lung carcinogen. NA induces cytotoxicity in airways following bioactivation by CYP (P450) enzymes. The overall goal of this study was to examine the relative contributions of hepatic and pulmonary CYPs to bioactivation, disposition and NA-induced pneumotoxicity in vivo. Substantial differences in the expression and enzymatic activity of P450s occur in various organs in human populations, which could modify susceptibility to NA-induced airway damage. The central hypothesis for this study was that NA has the potential to cause lung toxicity in humans and that the metabolism of …

Biomarkers And Metabolic Mechanisms Of Tobacco Smoke-Induced Lung Disease, Matthew Alan Hartog

Legacy Theses & Dissertations (2009 - 2024)

The overall goal of the research conducted in this dissertation is to determine the role of cytochrome (CYP) P450-mediated xenobiotic bioactivation in the development of tobacco smoke-induced lung toxicity. The central hypothesis of this work is that CYP-mediated bioactivation of specific tobacco smoke constituents is an important contributor to the generation of tobacco smoke-induced lung inflammation and injury. The specific aims are 1) to demonstrate that CYP-mediated metabolism contributes to the onset of lung inflammation following tobacco smoke inhalation; 2) to demonstrate that specific tobacco smoke constituents undergo CYP-mediated bioactivation in vivo; 3) to demonstrate that CYP-mediated bioactivation of tobacco …

Understanding The Genotoxicity Of Silver Nanoparticles And The Chemoprevention Of Pomegranate Extract, Sameera Nallanthighal

Legacy Theses & Dissertations (2009 - 2024)

The use of silver nanoparticles (AgNPs) in a wide variety of consumer products (i.e. toothpastes, food containers, dietary supplements and garments) for their antimicrobial properties can lead to potential oral exposure in humans. To enhance their stability, AgNPs are coated with capping agents such as citrate and polyvinylpyrrolidone (PVP). Despite the lack of significant general toxicity based on hematology, blood chemistry and histology evaluations, the potential genotoxic effects of AgNPs cannot be ruled out and have to be addressed. Studies examining the genotoxic risks of AgNPs are needed because genotoxicity is a strong indicator of cancer risk. Here we examined …

Effects Of Antibiotic Treatment On The Expression Of Hepatic And Intestinal Cytochrome P450, Bruno Pereira De Carvalho

Legacy Theses & Dissertations (2009 - 2024)

Expression of metabolic enzymes Cytochrome P450 (CYP) is highly affected by drugs, diseases, age and gender. The Intestinal microflora has been suggested to play a role in regulating CYP expression and antibiotic treatments would lead to changes in level and composition of microbiota in mouse gut. This study aims to analyze CYP expression changes in the liver and small intestine resulted from the reduction of intestinal microflora by antibiotics. Impacts on bile acid signaling were also analyzed for a better comprehension of the mechanisms involved in this modulation. Female C57BL/6J mice (9- to 13-week old) were treated with ampicillin (AMP) …

Endocrine-Disrupting Properties Of Pharmaceuticals And Personal Care Products (Ppcps): An Evaluation Using Aquatic Model Organisms, Manahil Monshi

Wayne State University Theses

Thousands of chemicals have introduced into the environment as a result of human activity since the industrial revolution, and the U.S. Government Accountability Office has estimated that as many as 1,500 new chemical entities are synthesized each year ("Key Issues: Toxic Chemicals - High Risk Issue," 2017). Many of these chemicals are now found in surface water and ground water and can have detrimental effects on environmental health and on human health. This anthropogenic contamination has resulted in the labeling of the diverse array of chemicals found in water, which are not routinely monitored or regulated, as contaminants of emerging …

A Multibiomarker Analysis Of Pollutant Effects On Atlantic Stingray Populations In Florida’S St. Johns River, John Whalen

UNF Graduate Theses and Dissertations

The goal of this study was to examine the potential health effects of organochlorine (OC) and polycyclic aromatic hydrocarbon (PAH) exposure on Atlantic stingray populations in Florida’s St. Johns River (SJR). Special emphasis was placed on identifying OC- and/or PAH-related effects in stingrays from areas of the lower (LSJR) and middle (MSJR) basins shown to possess elevated levels of these compounds, as well as characterizing baseline levels of pollutant exposure in the SJR shipping channel, which may be subjected to dredging in the near future, potentially resuspending and redistributing contaminated sediments and increasing pollutant-associated effects. To accomplish this, we measured …

Mercury Accumulation And Effects In The Brain Of Atlantic Sharpnose Sharks (Rhiszoprionodon Terranovae), Samantha L. Ehnert

UNF Graduate Theses and Dissertations

Sharks often bioaccumulate mercury (Hg) concentrations in their muscle to levels that threaten the health of human consumers. However, few published studies have examined if the high Hg levels seen in shark muscle also occur in the shark brain, or if Hg accumulation affects shark neurophysiology. Therefore, this study examined if shark brains accumulate significant levels of Hg, if Hg accumulation occurs in certain subcomponents of the brain, and if Hg accumulation is associated with oxidative stress effects on the shark central nervous system, with special focus on the Atlantic sharpnose shark (Rhizoprionodon terraenovae). Sharks were collected along …

Immunotherapy Against Drugs Of Abuse, Gianna Raimondi (Class Of 2017)

Writing Across the Curriculum

Current treatments for drug addiction involve classical pharmacological therapy, involving the use of competitive or noncompetitive agonists (full, partial, or inverse) and antagonists. Drugs of abuse enter the brain after crossing the blood-brain barrier rapidly and binding to the proper receptor(s). They are able to do so because they are small and lipid soluble, and produce reinforcing effects by increasing levels of dopamine in brain areas associated with reward. This occurs in specific systems associated with addiction. In the mesolimbic system, neuron cell bodies originate in the ventral tegmental area (VTA) and project to the nucleus accumbens (NAc), amygdala, hippocampus, …

The Effects Of Metolachlor Exposure On The Thp-1 Alveolar Monocyte And Macrophage Function, Jared S. Parmater

Dissertations and Theses @ UNI

The use of additive chemicals such as pesticides has become commonplace in agricultural practices in the Midwestern United States. Metolachlor, an herbicide used to regulate broadleaf weeds in corn and soybeans, is a widely utilized pesticide in the United States. This herbicide is effective in killing broadleaf weeds but has detrimental effects and consequences in non-target organisms. It is a frequent contaminant of ground water due to post application run-off and the air.

Inhalation constitutes one route of exposure, in addition to ingestion, adding to the list of unintended targets and consequences. This route of exposure creates an argument for …

From Disposable Culture To Disposable People: Teaching About The Unintended Consequences Of Plastics, Sasha Adkins

Antioch University Dissertations & Theses

Plastics, the epitome of disposable culture, pose both a toxicological and a spiritual problem. This dissertation examines plastics at a molecular level using the discourse of endocrine disruption, and at a sociological level using the discourses of eco-theology and environmental justice. Adding to the literature on the adsorption of toxicants to plastic marine debris, I demonstrate that certain types of plastic -- those containing mercaptans, such as styrene butadiene block copolymer -- efficiently concentrate methyl mercury from seawater. Further, samples of polycarbonate contributed mercury to seawater. I propose the term plastic-mediated magnification to describe the phenomenon that plastics, along with …

Effects Of Chromium On Mouse Splenic T Lymphocytes And Effects Of Ethanol Exposure During Early Neurodevelopment On Behaviors In Mice, Lu Dai

Theses and Dissertations--Toxicology and Cancer Biology

The dissertation consists of three major projects with the focus on the immunotoxicity of chromium and the behavior disorders caused by early ETOH exposure respectively.

Hexavalent chromium [Cr(VI)] is widely used in various industrial processes and has been recognized as a carcinogen. As the first line of host defense system, the immune system can be a primary target of Cr(VI). T cell population represents a major arm of the immune system that plays a critical role in host anti-tumor immunity. Dysfunction of T cells compromises host anti-tumor immunity resulting in oncogenesis. Using mouse splenic T cells as an in vitro …

Does Timing Of Herbicide Use Influence Rates Of Germination Or Seedling Biomass Of Native Plants Used For Restoration?, Christine Mcmanamen

Graduate Student Theses, Dissertations, & Professional Papers

Invasive plants can negatively impact native grasslands by changing their species composition, productivity, and function. Managers commonly use herbicides as a control method; however, this practice can lead to secondary invasion by other non-native invasive plants, unless measures are taken to promote natives. Because of this, managers often seed native plants after spraying herbicides. There is evidence, however, that chemical control of invasive plants may reduce the effectiveness of subsequent seed-addition treatments, but there is currently little quantitative information on optimal timing between spraying and seeding or on variation in herbicide sensitivity among native plants commonly used in seed mixes. …

Poison In Pink, Sydney V. Cook

Graduate Student Theses, Dissertations, & Professional Papers

Humans slather, spray, mist, and cleanse their bodies with personal care products like lotion, hairspray, cologne, and shampoo every day. Our cupboards are stocked full of them, but few of us understand what is in those jars and bottles. We trust that if it’s on the shelf at the store, it’s safe. However, this is not always the case, and many personal care products contain chemicals that are harmful to human and environmental health.

My multi-disciplinary Environmental Studies thesis project combines evidenced-based research, interviews, nonfiction narrative, and science communication to create part of a book manuscript intended to educate general …

Differential Gene Expression Analysis Of Metolachlor Treated Human Liver Cells By Microarray, Navinder Paul Kaur Brar

Dissertations and Theses @ UNI

Metolachlor is one of the most common pre-emergent pesticides used by Iowa farmers. It is used to control broadleaf weeds and grasses in the fields of corn and soybean. It is a frequent contaminant of groundwater and surface water due to runoff after application. It has been shown to inhibit protein and chlorophyll synthesis in plant cells, but its effect on mammalian cells has not been consistently conclusive. As metolachlor and other herbicides have been shown to be associated with harmful health effects in non-target organisms it is very important to determine a mechanism of action on non-target cells, especially …

Bioanalysis For Cocaine, Opiates, Methadone And Amphetamines Exposure Detection During Pregnancy, Marta Concheiro, Elena Lendoiro, Ana De Castro, Eva Gonzalez-Colmenero, Ana Concheiro-Guisan, Patricia Penas-Silva, Manuel Macias-Cortina, Angelines Cruz-Landeira, Manuel Lopez-Rivadulla

Publications and Research

Drug exposure during pregnancy constitutes a major legal issue and public health concern. Drug and metabolite determination in biological matrices from mother and newborn is an objective indication of prenatal drug exposure. However, limited data are available regarding the interpretation of these analytical results in terms of window of detection and degree of exposure. We collected paired maternal hair, meconium, placenta and umbilical cord from 727 mother-newborn dyads. We analyzed these specimens by liquid chromatography tandem mass spectrometry for the determination of cocaine, opioids, methadone and amphetamines, and compared the analytical results from the four different matrices. The cases were …

Identification Of “Kratom” (Mitragyna Speciosa) Alkaloids In Commercially Available Products, Julia Grzymkowski, Michelle R. Peace, Justin Poklis

Undergraduate Research Posters

“Kratom” is the common name for the botanical mitragyna speciosa. It is a tree native to Southeast Asia in which leaves contain the psychoactive alkaloids mitragynine and 7-hydroxymitragynine. Kratom is often ingested as teas, chewed, or smoked. It acts as a stimulant in small doses and as an opioid in large doses. Overdoses can result in vomiting, seizures, and death. Recently the Drug Enforcement Agency (DEA) placed Kratom on Schedule 1, but, due to public outcry, it was almost immediately removed.

Eleven kratom based products were obtained from various tobacco shops, “headshops” and via the internet including: Choice brand …