Toxicology Commons^™

A Validation Of The Detection Of Barbiturates In Hair By Elisa, Alisa M. Valentino

Student Theses

An original method to extract and detect barbiturates, specifically secobarbital, in hair by enzyme-linked immunosorbent assay (ELISA), has been developed. Drug-free hair specimens were fortified with an exaggerated amount of secobarbital to produce a homogeneous, true positive sample to be utilized to test the drug extraction efficiency from hair. Drug extraction using hair extraction buffer (HEB) from Immunalysis was compared to a base digestion using 1M NaOH. After LCMS/MS analysis, HEB extraction was deemed a successful method for extracting barbiturates from hair. Using this method, the Barbiturates Direct ELISA Kit from Immunalysis was evaluated for its potential use in the …

Quantitative Analysis Of Opioids And Cannabinoids In Wastewater Samples, Alethea Jacox

Student Theses

Wastewater-based epidemiology is an innovative approach that uses the analysis of human excretion products in wastewater to obtain information about exposure to drugs in defined population groups. We developed and validated an analytical method for the detection and quantification of opioids (morphine, oxycodone, hydrocodone, oxymorphone and hydromorphone), and cannabinoids (9-tetrahydrocannabinol, 11-nor 9-carboxy- tetrahydrocannabinol (THCCOOH) and THCCOOH-glucuronide) in raw influent wastewater samples by ultra-high performance liquid chromatography-tandem mass spectrometry. Method validation included linearity (5–1 000 ng/L for opioids, 10–1 000 ng/L for cannabinoids), imprecision (<21.2%), accuracy (83%–131%), matrix effect (from –35.1% to –14.7%) and extraction efficiency (25%–84%), limit of detection (1–5 ng/L) and quantification (5–10 ng/L) and auto-sampler stability (no loss detected). River, sewage overflow and wastewater samples were collected in triplicate from different locations in New York City and stored at -20 C until analysis. River water samples were negative for all the compounds. Water from sewage overflow location tested positive for morphine (10.7 ng/L), oxycodone (4.2–23.5 ng/L), oxymorphone (4.8 ng/L) and hydromorphone (4.2 ng/L). Wastewater samples tested positive for morphine (133.0– 258.3 ng/L), oxycodone (31.1– 63.6 ng/L), oxymorphone (16.0–56.8 ng/L), hydromorphone (6.8–18.0 ng/L), hydrocodone (4.0– 12.8 ng/L) and THCCOOH (168.2– 772.0 ng/L). This method is sensitive and specific for opioids and marijuana determination in wastewater samples.

Evaluation Of Perfluorohexane Sulfonate (Pfhxs) Exposure To Risk Of Liver Disease Caused By High Fat Fructose Diet, Dwight C. Anderson

Senior Honors Projects

Perfluorohexane sulfonate (PFHxS) has been used in products as surfactants[AS1] . These products include fluoropolymers and as protective and water-resistant coatings to different materials such as carpets, paper, and textiles. Also, evidence of PFHxS exposure has been reported in firefighters who use certain film forming foams. Current investigations have shown widespread exposure to PFHxS in the environment, specifically in drinking water. There has also been evidence of PFHxS accumulation in humans, with a half-life lasting several years.

PFHxS is one of several perfluoronated alkyl substances (PFAS). Other PFASs are considered to be hepatotoxic in rodents and potentially in humans. Studies …

Mercury Concentrations In Snowy Plovers And Sediments Of Their Breeding Environments In The Southern Great Plains, Laura Duffie

Electronic Theses and Dissertations

Western snowy plovers (Charadrius nivosus) are philopatric shorebirds sporadically distributed during the breeding season at saline lake and alkali flat breeding environments of the Southern Great Plains (SGP) of Oklahoma, New Mexico, and Texas. The major conservation threat to interior snowy plovers breeding on the SGP derives from anthropogenic modification of breeding environments. The SGP is one of the most intensively cultivated regions in the world, and excessive groundwater mining and resulting deterioration of artesian spring flows reduces site quantity and quality critical for regional successful nesting. Most saline lakes now primarily receive freshwater inputs via irregular precipitation …

Stability Of Synthetic Cathinones In Oral Fluid Samples, Briana Miller, Jiyoung Kim, Marta Concheiro

Publications and Research

Synthetic cathinones are new stimulant drugs derived from cathinone that have been sold as “legal highs” worldwide. These compounds can elicit powerful effects such as delusions, hallucinations as well as other potentially dangerous behavior. New analogs with varying effects and potencies are constantly introduced in the market to evade legislation, and they are not detected by routine screening and confirmation methods. Oral fluid is an alternative matrix of increasing interest in forensic toxicology. Its collection is non-invasive and easily supervised, and positive drug findings typically reflect recent drug exposure. The focus of this research was to develop a method for …

Chronic Toxicity Of Binary‐Metal Mixtures Of Cadmium And Zinc To Daphnia Magna, Edgar Pérez, Tham C. Hoang

School of Environmental Sustainability: Faculty Publications and Other Works

The present study characterized the chronic effect of binary‐metal mixtures of cadmium (Cd) and zinc (Zn) on Daphnia magna. The titration design was chosen to characterize the 21‐d chronic effects of the binary‐metal mixtures on survival, growth, reproduction, and metal accumulation in D. magna. Using this design, increasing concentrations of Zn (10, 20, 40, 80, 120, 160, and 200 μg/L) were titrated against a constant concentration of 1.5 μg/L Cd. The results demonstrated that Cd was highly toxic to D. magna. In a mixture with Cd and Zn, sublethal concentrations of 10 and 20 μg/L Zn were …

Physiological Effects Of Five Different Marine Natural Organic Matters (Noms) And Three Different Metals (Cu, Pb, Zn) On Early Life Stages Of The Blue Mussel (Mytilus Galloprovincialis), Lygia Sega Nogueira, Adalto Bianchini, Scott Smith, Marianna Basso Jorge, Rachael L. Diamond, Chris M. Wood

Chemistry Faculty Publications

Metals are present in aquatic environments as a result of natural and anthropogenic inputs, and may induce toxicity to organisms. One of the main factors that influence this toxicity in fresh water is natural organic matter (NOM) but all NOMs are not the same in this regard. In sea water, possible protection by marine NOMs is not well understood. Thus, our study isolated marine NOMs by solid-phase extraction from five different sites and characterized them by excitation-emission fluorescence analysis—one inshore (terrigenous origin), two offshore (autochthonous origin), and two intermediate in composition (indicative of a mixed origin). The physiological effects of …

The Optimization Of The Nuclear Protein In Testis (Nut) Antibody And Its Importance And Impact In The Pathology Lab, Lindsey Martinez

USF Tampa Graduate Theses and Dissertations

Optimization in immunohistochemistry is often a time consuming and complex process. There are a varying array of moving parts to consider all while preserving the sensitivity and specificity of the test. When optimizing an antibody it is important to consider the fixation of the tissue and the type of epitope retrieval that would be best suited for the test. The dilution of the primary antibody is a key marker for the efficiency and effectiveness of the laboratory protocol. The purpose of this study was to produce an optimized antibody for the nuclear protein in testis to detect NUT midline carcinoma …

A Compromised Liver Alters Polychlorinated Biphenyl-Mediated Toxicity, Banrida Wahlang, Jordan T. Perkins, Michael C. Petriello, Jessie B. Hoffman, Arnold J. Stromberg, Bernhard Hennig

Superfund Research Center Faculty Publications

Exposure to environmental toxicants namely polychlorinated biphenyls (PCBs) is correlated with multiple health disorders including liver and cardiovascular diseases. The liver is important for both xenobiotic and endobiotic metabolism. However, the responses of an injured liver to subsequent environmental insults has not been investigated. The current study aims to evaluate the role of a compromised liver in PCB-induced toxicity and define the implications on overall body homeostasis. Male C57Bl/6 mice were fed either an amino acid control diet (CD) or a methionine-choline deficient diet (MCD) during the 12-week study. Mice were subsequently exposed to either PCB126 (4.9 mg/kg) or the …

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 …