Pharmacology, Toxicology and Environmental Health Commons^™

Quantitative Structure-Activity Relationships For Polychlorinated Hydroxybiphenyl Estrogen Receptor Binding Affinity: An Assessment Of Conformer Flexibility, Steven P. Bradbury, Ovanes G. Mekenyan, Gerald T. Ankley

Steven P. Bradbury

A diverse group of xenobiotics has a high binding affinity to the estrogen receptor (ER), suggesting that it can accommodate large variability in ligand structure. Relationships between xenobiotic structure, binding affinity, and estrogenic response have been suggested to be dependent on the conformational structures of the ligands. To explore the influence of conformational flexibility on ER binding affinity, a quantitative structure—activity relationship (QSAR) study was undertaken with estradiol, diethylstilbestrol, and a set of polychlorinated hydroxybiphenyls (PCHBs) of environmental concern. Although the low-energy minima of the PCHB congeners suggested that interconversions among conformers were likely, the electronic parameters associated with the …

Research Needs For The Risk Assessment Of Health And Environmental Effects Of Endocrine Disruptors: A Report Of The Us Epa-Sponsored Workshop, Rj Kavlock, Gp Daston, C Derosa, P Fennercrisp, Le Gray, S Kaattari, Et Al

VIMS Articles

The hypothesis has been put forward that humans and wildlife species have suffered adverse health effects after exposure to endocrine-disrupting chemicals. Reported adverse effects include declines in populations, increases in cancers, and reduced reproductive function. The U.S. Environmental Protection Agency sponsored a workshop in April 1995 to bring together interested parties in an effort to identify research gaps related to this hypothesis and to establish priorities for future research activities. Approximately 90 invited participants were organized into work groups developed around the principal reported health effects-carcinogenesis, reproductive toxicity, neurotoxicity, and immunotoxicity--as well as along the risk assessment paradigm--hazard identification, dose-response …

Comparison Of Positive Screening And Confimatory Results From Federally Mandated Drug Testing Of Urine, Mary M. Stuck

Community & Environmental Health Theses & Dissertations

The purpose of this study was to analyze the accuracy of FDA approved immunoassays for the detection of drug positive urine samples.

Federal civilian employees are tested under the strict protocol of the Department of Health and Human Services mandatory guidelines for federal workplace drug testing programs. The guidelines provide for a two instrument testing protocol for the analysis of urine samples. The first is an FDA approved immunoassay. Samples which test positive on this screening immunoassay are then submitted for confirmatory testing with the "gold standard" gas chromatography/mass spectrometry.

Agency monthly drug testing summaries, required under the DHHS guidelines …

A Test Of An Alternate Calibration Matrix For Niosh Method 7300, Robert T. Vitek

Community & Environmental Health Theses & Dissertations

The purpose of this study was to determine if the analytical results (when determining cadmium, lead, and zinc concentrations) for air sample filters prepared and analyzed according to N:OSH Method 7300, differ significantly, from those obtained when the instrument is calibrated using EPA Method 200.7 acid matrix standards. The null hypothesis was that no statistically significant difference, measured at the 95% confidence level, would exist between results obtained from the two calibration standards. Careful standard and sample preparation, the use of an internal standard, and the application of working standard and working internal standard correction factors served to isolate the …

Estimating One-Electron Reduction Potentials Of Quinones, Steven P. Bradbury, Ovanes G. Mekenyan, V. B. Kamenska

Steven P. Bradbury

The one-electron reduction potential ∗ E1 7 of benzo-, naphtho-and anthracenequinones is related to their ability to undergo redox cycling and elicit cytotoxicity through oxidative stress. To evaluate a general approach to estimate the E1 7 of benzo-, naphtho-and anthracenequinones, QSAR approaches based on gas phase and solvation based methods were employed. Stereoelectronic descriptors of ground state quinones, respective intermediates of the redox cycle, and the di erences in parameters for the transition between intermediates were evaluated. The variation of E1 7 was correlated with descriptors of the parent quinones and speci c transition parameters. The energy of the highest …

2,3, 7,8-Tetrachlorodibenzo-P-Dioxin, Steven P. Bradbury

Steven P. Bradbury

Since 1985, the United States Environmental Protection Agency (USEPA) has classified 2,3,7,8-tetrachloro-p-dioxin (TCDD) as a probable human carcinogen; subsequently, sources of TCDD in the environment have been regulated on the basis of animal cancer rates extrapolated to doses associated with human exposures. Two major activities have prompted the decision to reassess this approach for evaluating TCDD toxicity and its associated risks. First, an epidemiological study of cancer mortality in U.S. chemical workers by the National Institute of Occupational Safety and Health provided evidence of TCDD-mediated human carcinogenicity (Fingerhut et al. 1991 ). Second, at a 1990 Banbury conference a consensus …

Acidic Marine Biotoxins Implicated In Diarrhetic Shellfish Poisoning, Eoin P. Carmody

Theses

An okadaic acid (OA) etiology has been demonstrated for most outbreaks of diarrhetic shellfish poisoning (DSP) in Europe, An isomer of OA, dinophysistoxin-2 (DTX-2), has recently been found in Irish waters and, in 1991 and 1994, was the major toxin during prolonged infestations in cultivated mussels (Mytilus edulis) along the south-west coast of Ireland.

The OA class of DSP toxins have been analysed by HPLC using modified versions of three established fluorescent derivatisation methods. A ‘dual tag’ method for the confirmation of specific toxins has also been developed.

Survey work has been carried out over the past four years on …

Expression Of The Xenobiotic Transporter P-Glycoprotein In The Mummichog (Fundulus Heteroclitus), Peter S. Cooper

Dissertations, Theses, and Masters Projects

The mammalian mdr1 P-glycoprotein (Pgp) has been implicated in xenobiotic resistance of drug-resistant cell lines and tumors, and may function in excretion or exclusion of toxic xenobiotics at several sites within the body. Pgp gene family members are expressed in excretory epithelia of several aquatic taxa and may contribute to the survival of pollution-tolerant aquatic animals in contaminated environments. For this reason the expression of Pgp family members was investigated in the livers and liver tumors of creosote-resistant mummichog (Fundulus heteroclitus) inhabiting a creosote-contaminated site (Atlantic Wood) in the Elizabeth River, Virginia. Expression of members of the Pgp gene family …

Demersal Predator Exposure To Toxic Organic Contaminants: Direct Effects Of Macrofauna In Trophic Transfer, Patrick Winfield Lay

Dissertations, Theses, and Masters Projects

The bioaccumulation and metabolism of organic contaminants (PAH, PCB) by three estuarine polychaetes, Nereis succinea (Frey and Leuckart 1847), Paraprionospio pinnata (Ehlers 1901) and Polydora ligni (Webster 1879), and by the fish predator, spot (Leiostomus xanthurus Lacepede 1802), were examined in laboratory experiments. Variations in trophic transfer of these contaminants resulting from differences in prey and contaminant type were also investigated. Toxicokinetic modeling reveals that metabolism of organic contaminants by invertebrate species result in variations in uptake, metabolism and elimination rate constants. Incorporation of prey metabolism potential in kinetic models increases the latter's predictability of biota-sediment accumulation factors (BSAFs), or …