Pharmacology, Toxicology and Environmental Health Commons^™

Can Acute Dermal Systemic Toxicity Tests Be Replaced With Oral Tests? A Comparison Of Route-Specific Systemic Toxicity And Hazard Classifications Under The Globally Harmonized System Of Classification And Labelling Of Chemicals (Ghs), Nigel P. Moore, David J. Andrew, Donald L. Bjerke, Stuart Creton, David Dreher, Thomas Holmes, Pilar Prieto, Troy Seidle, Tim G. Rowan

Troy Seidle, PhD

Acute systemic toxicity data (LD50 values) and hazard classifications derived in the rat following oral administration and dermal application have been analysed to examine whether or not orally-derived hazard classification or LD50 values can be used to determine dermal hazard classification. Comparing the oral and dermal classifications for 335 substances derived from oral and dermal LD50 values respectively revealed 17% concordance, and indicated that 7% of substances would be classified less severely while 76% would be classified more severely if oral classifications were applied directly to the dermal route. In contrast, applying the oral LD50 values within the dermal classification …

An Evaluation Of The Us High Production Volume (Hpv) Chemical-Testing Programme: A Study In (Ir)Relevance, Redundancy And Retro Thinking, Andrew Nicholson, Jessica Sandler, Troy Seidle

Troy Seidle, PhD

Under the US Environmental Protection Agency (EPA) High Production Volume (HPV) Challenge Programme, chemical companies have volunteered to conduct screening-level toxicity tests on approximately 2800 widely-used industrial chemicals. Participating companies are committed to providing available toxicity information to the EPA and presenting testing proposals for review by the EPA and posting on the EPA Web site as public information. People for the Ethical Treatment of Animals (PETA) and a coalition of animal protection organisations have reviewed all the test plans submitted by the participating chemical companies for compliance with the original HPV framework, as well as with animal welfare guidelines …

The Development Of New Concepts For Assessing Reproductive Toxicity Applicable To Large Scale Toxicological Programmes, S. Bremer, C. Pellizzer, S. Hoffmann, T. Seidle, T. Hartung

Troy Seidle, PhD

Large scale toxicological testing programmes which are currently ongoing such as the new European chemical legislation REACH require the development of new integrated testing strategies rather than applying traditional testing schemes to thousands of chemicals. The current practice of requiring in vivo testing for every possible adverse effect endanger the success of these programmes due (i) to limited testing facilities and sufficient capacity of scientific/technical knowledge for reproductive toxicity; (ii) an unacceptable number of laboratory animals involved (iii) an intolerable number of chemicals classified as false positive.

A key aspect of the implementation of new testing strategies is the determination …

A Modular One-Generation Reproduction Study As A Flexible Testing System For Regulatory Safety Assessment, Richard Vogel, Troy Seidle, Horst Spielmann

Troy Seidle, PhD

The European Union’s Registration, Evaluation and Authorisation of Chemicals (REACH) legislation mandates testing and evaluation of approximately 30,000 existing substances within a short period of time, beginning with the most widely used “high production volume” (HPV) chemicals. REACH testing requirements for the roughly 3000 HPV chemicals specify three separate tests for reproductive toxicity: two developmental toxicity studies on different animal species (OECD Test Guideline 414) and a two-generation reproduction toxicity study (OECD TG 416). These studies are highly costly in both economic and animal welfare terms. OECD TG 416 is a fertility study intended to evaluate reproductive performance of animals …

Response Of Soil Nitrification To The Veterinary Pharmaceuticals Monensin, Ivermectin And Zinc Bacitracin, Magda A. Konopka

Electronic Thesis and Dissertation Repository

Pharmaceutical residues can reach agricultural land through amendment with animal or human waste. Since 2010, a series of replicated plots received annual applications of ivermectin, monensin and zinc bacitracin, either singly or in a mixture, at 0.1 mg/kg and 10 mg/kg concentrations. I collected soil samples before and after the fourth annual application of pharmaceuticals and assayed them for functional changes and amoA gene abundance, a gene needed for ammonia oxidation. In 2013, I exposed the soils to 100 mg/kg in a laboratory experiment which resulted in acceleration of nitrification. Under 10 mg/kg treatments in the field the abundance of …

Interactive Effects Of Climate Change With Nutrients, Mercury, And Freshwater Acidification On Key Taxa In The North Atlantic Landscape Conservation Cooperative Region, Alfred E. Pinkey, Charles T. Driscoll, David C. Evers, Michael J. Hooper, Jeffrey Horan, Jess W. Jones, Rebecca S. Lazarus, Harold G. Marshall, Andrew Milliken, Barnett A. Rattner, John Schmerfold, Donald W. Sparling

Biological Sciences Faculty Publications

The North Atlantic Landscape Conservation Cooperative LCC (NA LCC) is a public-private partnership that provides information to support conservation decisions that may be affected by global climate change (GCC) and other threats. The NA LCC region extends from southeast Virginia to the Canadian Maritime Provinces. Within this region, the US National Climate Assessment documented increases in air temperature, total precipitation, frequency of heavy precipitation events, and rising sea level, and predicted more drastic changes. Here, we synthesize literature on the effects of GCC interacting with selected contaminant, nutrient, and environmental processes to adversely affect natural resources within this region. Using …

Utilizing Indicator Of Reduction In Soils Tubes To Affirm A Serpentinitic Hydric Soil On The California Central Coast, Jason Demoss

Natural Resources Management and Environmental Sciences

Wetlands are vital ecosystems that are crucial in maintaining the life of rare and unique soils, plants, and animals. These ecosystems are key players in water storage, water filtration, carbon storage, and harboring unique species. Since the intervention of human development on the Earth’s surface, almost 50% of the Earth’s original wetlands have either been damaged or destroyed. The identification and assessment of both new and old wetlands is crucial in the survival of these precious ecosystems and their conservation. A 3 month-long study was performed to confirm the hydric status of a soil derived from serpentinitic parent material. The …

Discovery Of Thienoquinolone Derivatives As Selective And Atp Non-Competitive Cdk5/P25 Inhibitors By Structure-Based Virtual Screening, Arindam Chatterjee, Stephen J. Cutler, Robert J. Doerksen, Ikhlas A. Khan, John S. Williamson

Office for Research Publications and Presentations

Calpain mediated cleavage of CDK5 natural precursor p35 causes a stable complex formation of CDK5/p25, which leads to hyperphosphorylation of tau. Thus inhibition of this complex is a viable target for numerous acute and chronic neurodegenerative diseases involving tau protein, including Alzheimer’s disease. Since CDK5 has the highest sequence homology with its mitotic counterpart CDK2, our primary goal was to design selective CDK5/p25 inhibitors targeting neurodegeneration. A novel structure-based virtual screening protocol comprised of e-pharmacophore models and virtual screening workflow was used to identify nine compounds from a commercial database containing 2.84 million compounds. An ATP non-competitive and selective thieno[3,2- …

Inhalable Constituents Of Thirdhand Tobacco Smoke: Chemical Characterization And Health Impact Considerations, Mohamad Sleiman, Jennifer M. Logue, Wentai Luo, James F. Pankow, Lara A. Gundel, Hugo Destaillats

Chemistry Faculty Publications and Presentations

Tobacco smoke residues lingering in the indoor environment, also termed thirdhand smoke (THS), can be a source of long-term exposure to harmful pollutants. THS composition is affected by chemical transformations and by air–surface partitioning over time scales of minutes to months. This study identified and quantified airborne THS pollutants available for respiratory exposure, identified potential environmental tracers, and estimated health impacts to nonsmokers. In a ventilated 18 m3 laboratory chamber, six cigarettes were machine-smoked, and levels of particulate matter (PM2.5) and 58 volatile organic compounds (VOCs) were monitored during an aging period of 18 h. Results were compared with field …

Ligand-Receptor Interactions For Supramolecular Disassembly With Applications In Screening And Drug Delivery, Diego Amado Torres

Doctoral Dissertations

Proteins have the capacity to bind specific sets of compounds known as ligands, these are small molecules with a recurrent theme in their molecular design that is a characteristic exploited here to (i) identify particular affinities of small molecules for proteins with the aim of using them as ligands, inhibitors, or targeting moieties in more complex systems by means of a methodology that screens small molecules based on protein affinity; (ii) decorate a self-assembling supramolecular system at different positions, making it responsive to a complementary protein with the aim of exploring differences in disassembly and sensitivity of the release of …

Application Of A Bioenergetics Framework For Assessing Sub-Lethal Effects Of Pollutants In The Freshwater Mussel Elliptio Complanata, Christopher G. Goodchild

All Theses And Dissertations

Although biomarkers are frequently used to assess sublethal effects of contaminants, a lack of mechanistic linkages to higher-level effects limits the predictive power of biomarkers. Bioenergetics has been proposed as a framework for linking cellular effects to whole-animal effects. We investigated sublethal effects of exposure to wastewater treatment facility effluent in freshwater mussels in situ, thereby capturing ecologically relevant exposure conditions. Our study focused on the energetic biomarker AMP-activated protein kinase (AMPK), while also considering more traditional biomarkers like heat shock proteins (HSP70), and antioxidant enzymes (i.e., superoxide dismutase (SOD), glutathione-S-transferase (GST)). We examined biomarkers at mRNA and protein levels. …

Light Pollution Research Through Citizen Science, John Kanemoto

STAR Program Research Presentations

Light pollution (LP) can disrupt and/or degrade the health of all living things, as well as, their environments. The goal of my research at the NOAO was to check the accuracy of the citizen science LP reporting systems entitled: Globe at Night (GaN), Dark Sky Meter (DSM), and Loss of the Night (LoN). On the GaN webpage, the darkness of the night sky (DotNS) is reported by selecting a magnitude chart. Each magnitude chart has a different density/number of stars around a specific constellation. The greater number of stars implies a darker night sky. Within the DSM iPhone application, a …

Effects Of Contaminated St. Lucie River Saltwater Sediments On An Amphipod (Ampelisca Abdita) And A Hard-Shell Clam (Mercenaria Mercenaria), Tham C. Hoang, Gary M. Rand

School of Environmental Sustainability: Faculty Publications and Other Works

The St. Lucie estuary (SLE) ecosystem in South Florida has been shown to be contaminated with metals and pesticides. Our earlier studies also showed that aquatic organisms, especially benthic species in the SLE ecosystem, might be potentially at high risk from copper (Cu) exposure. The objectives of this study were to conduct studies with separate groups of organisms exposed to seven field-collected sediment samples from the St. Lucie River according to standard procedures to evaluate toxicity and tissue concentrations of Cu and zinc (Zn). Short term and longer term whole sediment acute toxicity studies were performed with Ampelisca abdita and …

Exposure To Traffic Pollution, Acute Inflammation And Autonomic Response In A Panel Of Car Commuters, Jeremy A. Sarnat, Rachel Golan, Roby Greenwald, Amit U. Raysoni, Priya Kewada, Andrea Winquist, Stefanie E. Sarnat, W. Dana Flanders, Maria C. Mirabelli, Jennifer E. Zora

School of Earth, Environmental, and Marine Sciences Faculty Publications and Presentations

Background

Exposure to traffic pollution has been linked to numerous adverse health endpoints. Despite this, limited data examining traffic exposures during realistic commutes and acute response exists. Objectives: We conducted the Atlanta Commuters Exposures (ACE-1) Study, an extensive panel-based exposure and health study, to measure chemically-resolved in-vehicle exposures and corresponding changes in acute oxidative stress, lipid peroxidation, pulmonary and systemic inflammation and autonomic response.

Methods

We recruited 42 adults (21 with and 21 without asthma) to conduct two 2-h scripted highway commutes during morning rush hour in the metropolitan Atlanta area. A suite of in-vehicle particulate components were measured in …

Investigation Into The Control Of Melittin Secondary Structure And Antimicrobial Activity, Zachary B. Molinets

Open Access Theses

Antimicrobial resistance has been an exponentially growing problem since the discovery of antibiotics. Antibiotics have been misused for many years and this misuse has grown into a real problem for the medical community. While there are countless safeguards to prevent infection by a resistant strain of bacteria, there are still many plagued by it and must be treated with sometimes dangerous antibiotics. Melittin, along with many other peptides, contain potent antimicrobial properties, but are also toxic toward enthrocytes. The control of the secondary structure of peptides provides the key to adjusting their activity.

A Comparative Study Of Gupix And Geopixe Software In The Analysis Of Pixe Spectra Of Aerosol Samples, Sean Collison

Honors Theses

Proton-induced X-ray emission (PIXE) spectroscopy is a powerful tool used in the Union College Ion-Beam Analysis Laboratory for the elemental analysis of environmental pollution. Samples are bombarded with proton beams from the 1.1‐MV Pelletron accelerator and characteristic X-rays emitted from the samples are detected, resulting in X-ray energy spectra. These spectra are analyzed using software packages that fit the data and calculate the concentrations of elements in the samples. I have performed a comparative study of two of the most popular software packages, GUPIX and GeoPIXE, in the analysis of atmospheric aerosol samples to assess the strengths and weaknesses of …

Ligand-Receptor Interactions For Supramolecular Disassembly With Applications In Screening And Drug Delivery, Diego F. Amado Torres

Diego Amado Torres

Proteins have the capacity to bind specific sets of compounds known as ligands, these are small molecules with a recurrent theme in their molecular design that is a characteristic exploited here to (i) identify particular affinities of small molecules for proteins with the aim of using them as ligands, inhibitors, or targeting moieties in more complex systems by means of a methodology that screens small molecules based on protein affinity; (ii) decorate a self-assembling supramolecular system at different positions, making it responsive to a complementary protein with the aim of exploring differences in disassembly and sensitivity of the release of …

Statistical Analysis, Modeling, And Algorithms For Pharmaceutical And Cancer Systems, Bong-Jin Choi

USF Tampa Graduate Theses and Dissertations

The aim of the present study is to develop a statistical algorithm and model associ- ated with breast and lung cancer patients. In this study, we developed several statistical softwares, R packages, and models using our new statistical approach.

In the present study, we used the five parameters logistic model for determining the optimal doses of a pharmaceutical drugs, including dynamic initial points, an automatic process for outlier detection and an algorithm that develops a graphic user interface(GUI) program. The developed statistical procedure assists medical scientists by reducing their time in determining the optimal dose of new drugs, and can …

Bioplastics: Reinventing Conventional Plastic Production And The Future Of Biodegradable Materials, Ruby Roca

2014 Student Theses

The use of plastic is prevalent in our society due to the increasing amount of new products entering the market that need some form of packaging that is solid enough yet disposable. From everything to yogurt containers to diapers, plastic containers are a large part of our society’s consumption culture and often goes unnoticed. However, people point to plastic water bottles and containers as the only culprit, and often times forget that almost all packaging contains some form of plastic. For my thesis I want to examine how the use of plastics has increased waste material, considering that it takes …

Candy Flavorings In Tobacco, Jessica E. Brown, Wentai Luo, Lorne M. Isabelle, James F. Pankow

Chemistry Faculty Publications and Presentations

Professor James F. Pankow reveals striking similarities between the patterns in the flavoring chemicals used in flavored tobacco products and those in popular candy and Kool-Aid products. The authors analyzed 12 artificially flavored candy and fruit drink products and compared them to 15 widely-available flavored tobacco products. They found significant overlap in the chemical signatures of the flavor chemicals. Several of the tobacco products contained flavor chemicals at much higher concentrations than in the non-tobacco products.

Water Water Everywhere: Analyzing Long Island's Water Issues And Finding Solutions For A Sustainable Future, Anthony T. Becker

2014 Student Theses

Over three million people call Long Island their home. With access to beautiful landscapes, world-renowned beaches, and proximity to New York City, it is no wonder that so many proudly call this geographic stretch of glacial till their home. However, throughout the years our actions do not necessarily reflect this affection we have to our home. Years of sprawl and human infestation across the island have resulted in widespread environmental degradation. Specifically, the water we drink and the beaches we enjoy have become endangered. I plan on studying the urban ecology of how intensified population growth led to the eutrophication …

Health Hazards In Rental Housing: An Overview Of Clark County, Nevada, Amanda Nicole Sokolowsky

UNLV Theses, Dissertations, Professional Papers, and Capstones

A wide range of health conditions are associated with housing conditions, including asthma, respiratory infections, injuries, mental health issues, and lead poisoning. People in modern societies spend more than 90% of their time indoors, the vast majority of which is spent at home. Therefore, any new information on housing related health hazards in a population provides an opportunity for a new prevention program. Reports have shown that rental properties have more health related hazards than owner occupied housing, and rental properties are frequently occupied by low-income and minority individuals. This descriptive study intended to provide an overview of housing related …

Evaluating The Impact Of A Home-~Based Childhood Asthma Intervention Program In Clark County, Nevada, Mackenzie Suzanne Burns

UNLV Theses, Dissertations, Professional Papers, and Capstones

Asthma is a chronic, incurable, costly, and potentially life–threatening disease that affects an estimated 7 million children in the United States; further, more than 56,000 Nevada children are currently living with asthma. The literature suggests that a number of factors that contribute to either the development of asthma or the exacerbation of asthma symptoms in sensitive individuals can be traced to the home environment. Given that the majority of Americans spend over 90% of their time indoors, of which two–thirds are spent at home, a home–based childhood asthma intervention program represents a unique primary prevention opportunity. This pre–experimental study evaluated …

Development Of A Molecular Method For Detecting The Causative Agent Of Swimmer's Itch (Trichobilharzia) In Freshwater Ecosystems, Heidi Mcmaster

UNLV Theses, Dissertations, Professional Papers, and Capstones

Cercarial dermatitis, commonly known as swimmer's itch, is caused by penetration of larvae of the schistosome,Trichobilharzia, into the dermis and epidermis layers of the skin. Symptoms are characterized by painful swelling and itching at the site of penetration. The normal hosts for the life cycle of the schistosome are aquatic birds and aquatic snails. The most frequently used method of detection forTrichobilharziais microscopy. With increases in the occurrence of cercarial dermatitis outbreaks in freshwater in the Southwestern United States, it is becoming increasingly important to develop and standardize a molecular method for rapid detection that can assist health professionals and …

Effects Of Urban Stream Burial On Organic Matter Dynamics And Reach Scale Nitrate Retention, Jake J. Beaulieu, Paul M. Mayer, Sujay S. Kaushal, Michael J. Pennino, Clay P. Arango, David A. Balz, Timothy J. Canfield, Colleen M. Elonen, Ken M. Fritz, Brian H. Hill, Hodon Ryu, Jorge W. Santo Domingo

All Faculty Scholarship for the College of the Sciences

Nitrogen (N) retention in streams is an important ecosystem service that may be affected by the widespread burial of streams in stormwater pipes in urban watersheds. We predicted that stream burial suppresses the capacity of streams to retain nitrate (NO₃ ⁻) by eliminating primary production, reducing respiration rates and organic matter availability, and increasing specific discharge. We tested these predictions by measuring whole-stream NO₃ ⁻ removal rates using ¹⁵NO₃ ⁻ isotope tracer releases in paired buried and open reaches in three streams in Cincinnati, Ohio (USA) during four seasons. Nitrate uptake lengths were 29 times …

Pharmaceuticals And Personal Care Products: Emerging Contaminants In Aquatic Ecosystems, Jenny E. Zenobio

Open Access Theses

In recent years, the presence of pharmaceuticals and personal care products (PPCPs) in aquatic systems has led to research on their fate and effects. PPCPs have been found in mixture in wastewater effluents, surface, ground, and drinking water at low concentrations from areas of intense urbanization. Although adverse effects to human health from the current environmental concentrations are unlikely, the impacts to ecological receptors are not clear. We performed field and laboratory studies to quantify and evaluate effects of PPCPs on fish. First, a field study was conducted at the Baca National Wildlife Refuge, Colorado (2010-2012) because a portion of …

Speciation, Metabolism, Toxicity, And Protein-Binding Of Different Arsenic Species In Human Cells, Szabina A. Stice

FIU Electronic Theses and Dissertations

Despite of its known toxicity and potential to cause cancer, arsenic has been proven to be a very important tool for the treatment of various refractory neoplasms. One of the promising arsenic-containing chemotherapeutic agents in clinical trials is Darinaparsin (dimethylarsinous glutathione, DMA^III(GS)). In order to understand its toxicity and therapeutic efficacy, the metabolism of Darinaparsin in human cancer cells was evaluated. With the aim of detecting all potential intermediates and final products of the biotransformation of Darinaparsin and other arsenicals, an analytical method employing high performance liquid chromatography inductively coupled mass spectrometry (HPLC-ICP-MS) was developed. This method was …

20 Things You Can Do To Conserve Energy In 2015, Lissa Coffey

LissaCoffey

Energy is lost when air conditioners and hot-air furnaces have to work harder to draw air through dirty filters. Cleaning/replacing a dirty air conditioner filter can save 5 percent of the energy used. That could save 175 pounds of CO2.air filters can save your company up to 30% of your total HVAC energy spend and last twice as long as traditional air filters. Also your company will benefit from significantly reduced installation labor costs and waste disposal costs. In the average commercial building, 50% of the energy bill is for the HVAC system and 30% of that is directly related …

Species - Dependent Cardiac And Motor Responses To Cholinergic Stimulation In Daphnia Pulex And Daphnia Magna, Bryan James Hannan

Wayne State University Theses

The role of acetylcholine (ACh) in regulating the activity of the heart and `feeding current' driven by the beating thoracic appendages of Daphnia pulex and Daphnia magna was evaluated using acetylcholinesterase inhibitors (AChE-I) and muscarinic receptor agonists. Single animals, tethered to a stainless steel pin, were tested in a watertight aquatic chamber that allowed free movement of appendages and swimming antennae. Heart contraction rate and the rate of thoracic appendage beating were quantified optically by measuring fluctuating changes in light-intensity caused by movement. Physostigmine, neostigmine, oxotremorine, pilocarpine as well as nicotine were used to study ACh and AChE. Atropine was …

Synthesis And Characterization Of Brain Penetrant Prodrug Of Neuroprotective D264: Potential Disease Modifying Treatment Agent For Parkinson's Disease, Fahd Shamoon Dholkawala

Wayne State University Theses

Parkinson's disease (PD) is a complex neurodegenerative disorder with progressive loss of dopamanergic neurons in the substantia nigra region of the brain and accumulation of intracytoplasmic inclusions called `Lewy bodies'. PD is characterized by tremors, rigidity, slowness of movement, bradykinesia and postural imbalances. Although the etiology of PD is not well understood, it is well established that oxidative stress, mitochondrial dysfunction, alpha-synuclein aggregation play a central role in the pathogenesis of PD. Current treatment methods are based on symptomatic relief without addressing the underlying pathophysiological factors responsible for the disease. It is important to develop therapies which can address these …