Pharmacology, Toxicology and Environmental Health Commons^™

Deterministic Intracellular Modeling, Jacqueline B. Young

Theses and Dissertations

The United States Air Force is interested in the potential side effects at the cellular level from exposure to mission-essential chemicals. Presently, Air Force toxicology studies are conducted to help shed light in identifying potential hazards to workers. However, it takes a considerable amount of money, resources, and time to obtain and analyze experimental results from toxicology studies. The necessity for innovative methods that enable researchers to more effectively generate and analyze data is apparent.

Stochastic Intra-Cellular Modeling, Thomas E. Hopkins

Theses and Dissertations

Air Force personnel may sometimes come into contact with potentially harmful chemicals while performing their duties. Of course the Air Force desires to keep any potential health risks to its members to a minimum. To this end the Air Force would like to identify which chemicals are toxic, their level of toxicity, and the processes by which these chemicals disrupt normal biological activities at the cellular level. The development of mathematical models can be of great benefit to toxicity studies. Because real world systems involve randomness, that is noise, and the desire is to create mathematical models to represent those …

Overview Of Data And Conceptual Approaches For Derivation Of Quantitative Structure-Activity Relationships For Ecotoxicological Effects Of Organic Chemicals, Steven P. Bradbury, Christine L. Russom, Gerald T. Ankley, T. Wayne Schultz, John D. Walker

Steven P. Bradbury

The use of quantitative structure–activity relationships (QSARs) in assessing potential toxic effects of organic chemicals on aquatic organisms continues to evolve as computational efficiency and toxicological understanding advance. With the everincreasing production of new chemicals, and the need to optimize resources to assess thousands of existing chemicals in commerce, regulatory agencies have turned to QSARs as essential tools to help prioritize tiered risk assessments when empirical data are not available to evaluate toxicological effects. Progress in designing scientifically credible QSARs is intimately associated with the development of empirically derived databases of well-defined and quantified toxicity endpoints, which are based on …

Qsar Prioritization Of Chemical Inventories For Endocrine Disruptor Testing, Steven P. Bradbury, Patricia Schmeider, Ovanes Mekenyan, Gilman Veith

Steven P. Bradbury

Binding affinity between chemicals and the estrogen receptor (ER) serves as an indicator of the potential to cause endocrine disruption through this receptor-mediated endocrine pathway. Estimating ER-binding affinity is, therefore, one strategic approach to reducing the costs of screening chemicals for potential risks of endocrine disruption. While measuring ER binding with in vitro assays may be the first choice in prioritizing chemicals for additional in vitro or in vivo estrogenicity testing, the time and costs associated with screening thousands of chemicals is prohibitive. Recent advances in 3D modeling of the reactivity of flexible structures make in silico methods for estimating …

An Overview Of The Use Of Quantitative Structure-Activity Relationships For Ranking And Prioritzing Large Chemical Inventories For Environmental Risk Assessments, Steven P. Bradbury, Christine L. Russom, Roger L. Breton, John D. Walker

Steven P. Bradbury

Ecological risk assessments for chemical stressors are used to establish linkages between likely exposure concentrations and adverse effects to ecological receptors. At times, it is useful to conduct screening risk assessments to assist in prioritizing or ranking chemicals on the basis of potential hazard and exposure assessment parameters. Ranking of large chemical inventories can provide evidence for focusing research and/or cleanup efforts on specific chemicals of concern. Because of financial and time constraints, data gaps exist, and the risk assessor is left with decisions on which models to use to estimate the parameter of concern. In this review, several methods …

Influence Of Suspended Solids On Acute Toxicity Of Carbofuran To Daphnia Magna: Ii. An Evaluation Of Potential Interactive Mechanisms, Steven P. Bradbury, Carl Herbrandson, Deborah L. Swackhamer

Steven P. Bradbury

It has been demonstrated that simultaneous exposure of Daphnia magna to suspended solids and a carbamate pesticide potentiates the toxic response to the pesticide. The toxicodynamics between these stressors were investigated to determine possible mechanisms of interaction. Three experimental series were conducted with D. magna to determine: the effect of food availability on carbofuran toxicity; the effect of food availability on jointly administered carbofuran and suspended solids; and changes in the magnitude of effects which can occur with suspended solids of different composition. These experiments demonstrated that both carbofuran toxicity and the joint toxicity of carbofuran and suspended solids to …

Quantitative Structure-Activity Relationship Models For Prediction Of Estrogen Receptor Binding Affinity Of Structurally Diverse Chemicals, Steven P. Bradbury, Patricia K. Schmeider, Gerald Ankley, Ovanes Mekenyan, John D. Walker

Steven P. Bradbury

The demonstrated ability of a variety of structurally diverse chemicals to bind to the estrogen receptor has raised the concern that chemicals in the environment may be causing adverse effects through interference with nuclear receptor pathways. Many structure–activity relationship models have been developed to predict chemical binding to the estrogen receptor as an indication of potential estrogenicity. Models based on either two-dimensional or three-dimensional molecular descriptions that have been used to predict potential for binding to the estrogen receptor are the subject of the current review. The utility of such approaches to predict binding potential of diverse chemical structures in …

Influence Of Suspended Solids On Acute Toxicity Of Carbofuran To Daphnia Magna: I. Interactive Effects, Steven P. Bradbury, Carl Herbrandson, Deborah L. Swackhamer

Steven P. Bradbury

This study explored the effects on Daphnia magna from exposure to the pesticide carbofuran in combination with stress from suspended solids exposure. Our objective was to assess whether suspended solids affects the toxicodynamic response of D. magna to carbofuran. A series of laboratory experiments was performed where animals were exposed to carbofuran concentrations ranging from 0 to 160 mg/l in combination with suspended solids concentrations ranging from 0 to 10,000 mg/l. In the absence of suspended solids, effects of carbofuran were dose dependent and resulted in an EC(sub)50 of 92 mg/l. Exposure to suspended solids, up to extreme levels that …

Analysis Of Phycotoxin And Mycotoxin, Contaminants In Foods, Using Liquid Chromatography - Mass Spectrometry Techniques, Ana Brana Magdalena

Theses

The impact of phycotoxins and mycotoxins on human and animal health are of important concern for worldwide authorities and the scientific community. Liquid chromatography-mass spectrometry (LC-MS) techniques have been developed, optimised and validated for the analysis of these toxins.

Phycotoxins are potentially toxic substances, which are produced by marine phytoplankton and which may accumulate in shellfish or finfish. Azaspiracid poisoning (AZP) is a recently discovered syndrome that has been implicated in several incidents of human intoxications. A study was undertaken to examine the distribution of azaspiracids (AZA) in scallops {Pecten maximiis) and mussels {Mytiliis edulis). Domoic acid (DA) is an …

Recognizing Toxic Species In Aquatic Habitats: A Potential Concern In Lake Management, Mikolaj Kokocinski, Harold G. Marshall

Biological Sciences Faculty Publications

The importance of distinguishing toxic and non-toxic algal species is becoming a more common problem for management decisions associated with various freshwater and estuarine habitats. An example is given where two dinoflagellates, originally unidentified as closely resembling the toxin producing Pfiesteria spp., have been compared to these species. In order to clarify any relationship to Pfiesteria spp., scanning electron microscopy was used to determine the plate tabulation patterns of these dinoflagellates and make comparisons to the tabulation present in Pfiesteria spp. The results indicated significant differences in the plate tabulations of these taxa to distinguish them from Pfiesteria …