A three-part project was devised to investigate the origins of and potential methods to reduce the risk of occupational exposure to cytotoxic drugs. The first phase involved researching the current decontamination methods applied in UK hospital pharmacies, which manipulate cytotoxic drugs. The second phase evaluated practical decontamination methods, and the third phase investigated one intervention aimed at reducing or preventing contamination occurring in an isolator. A questionnaire was sent out to ASU managers in NHS hospital pharmacies to gain information about the disinfection and decontamination procedures and products used. The practical decontamination methods investigated were mechanical removal and degradation by detergents (pH range from 1.7 - 13.2) and cleaning agents, and degradation by vaporised hydrogen peroxide. Analytical methods were developed and validated to recover and quantify the amount of cytotoxic marker drug remaining after the decontamination tests carried out in phase two, and to recover and quantify cytotoxic surface contamination from various surfaces in phase three of this work. This composed an attempt to evaluate the effectiveness of a closed-system e.g. PhaSeal® device for fluid-transfer, in reducing contamination produced from the compounding of cytotoxic drugs in an isolator. The detergents and cleaning agents were effective in removing or reducing cytotoxic surface contamination. Alkaline detergents caused degradation of doxorubicin (maximum 81% at pH 13.2 after 1 hour exposure); the other detergents tested did not xi x degrade the cytotoxic drugs investigated. Exposure to vaporised hydrogen peroxide (1.6g min-1 for 2 hours) caused the degradation of cyclophosphamide (98.9%), 5-Fluorouracil (29.3%), doxorubicin (71.0%) and epirubicin (65.9%) when exposed in pharmaceutical diluents. The closed-system (PhaSeal®) device was effective in reducing contamination produced in an isolator from the compounding of cytotoxic drugs. The risk posed by handling and manipulation of cytotoxic drugs and products to the operator and the environment may be reduced, if not eliminated by considering additional approaches to the methods already in place. Firstly, the application of effective decontamination methods; and secondly, by using an effective closed-system, for example the PhaSeal® drug transfer device in a controlled environment.

by Wai Yin Karen Fong. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1996. / Includes bibliographical references (leaves [106]-[110]). / Abstract --- p.2 / Acknowledgments --- p.3 / Dedication --- p.4 / Abbreviations --- p.5 / Table of Contents --- p.7 / Chapter Chapter 1: --- Introduction --- p.11 / Chapter 1.1 --- Overviews of packaging materials --- p.11 / Chapter 1.2 --- Source of contamination --- p.14 / Chapter 1.2.1 --- Contamination from packaging materials --- p.15 / Chapter 1.2.2 --- Contamination of plasticisers from packaging materials and its effect --- p.16 / Chapter 1.3 --- Classification of commercial plasticisers --- p.19 / Chapter 1.3.1 --- Application of plasticisers --- p.20 / Chapter 1.4 --- Analysis of the plasticisers in the food packaging films --- p.22 / Chapter 1.5 --- Analysis of plasticisers in food using isotope dilution technique --- p.22 / Chapter Chapter 2 --- : Instrumentation and Analytical methods --- p.25 / Chapter 2.0 --- Instrumentation --- p.25 / Chapter 2.1 --- Gas chromatography --- p.25 / Chapter 2.2 --- Detector --- p.26 / Chapter 2.2.1 --- Flame ionisation detector --- p.26 / Chapter 2.2.2 --- Mass spectrometer --- p.27 / Chapter 2.2.2.1 --- Ion trap detector --- p.28 / Chapter 2.2.3 --- Ionisation mode --- p.33 / Chapter 2.2.3.1 --- Electron ionisation (EI) --- p.33 / Chapter 2.2.3.2 --- Chemical ionisation (CI) --- p.34 / Chapter 2.4 --- Analytical methods --- p.36 / Chapter 2.3 --- The use of combined GC/MS in the analysis of plasticisers --- p.36 / Chapter 2.3.1 --- Identification by GC/MS --- p.37 / Chapter 2.3.2 --- Qualitative MS --- p.37 / Chapter 2.3.3 --- Quantitative MS --- p.39 / Chapter 2.3.3.1 --- Isotope dilution technique --- p.40 / Chapter Chapter 3: --- Analysis of plasticisers in food packaging materials --- p.41 / Chapter 3.1 --- Introduction --- p.41 / Chapter 3.2 --- Experimental and Instrumental --- p.42 / Chapter 3.2.1 --- Reagents --- p.43 / Chapter 3.2.2 --- Materials --- p.43 / Chapter 3.3 --- Identification of food packaging materials --- p.43 / Chapter 3.3.1 --- Fourier transform infrared spectrometry --- p.44 / Chapter 3.3.2 --- Burning test --- p.45 / Chapter 3.3.3 --- Solvent dissolution method --- p.46 / Chapter 3.4 --- Extraction of plasticisers from the packaging materials --- p.49 / Chapter 3.4.1 --- Chloroform extraction --- p.50 / Chapter 3.4.2 --- Solvent reflux method --- p.50 / Chapter 3.5 --- Results and discussion --- p.51 / Chapter 3.5.1 --- Precision test --- p.51 / Chapter 3.5.2 --- Calibration curve --- p.52 / Chapter 3.5.3 --- Detection limit --- p.54 / Chapter 3.5.4 --- Recovery --- p.54 / Chapter 3.6 --- Survey of the level of plasticisers in food packaging materials --- p.55 / Chapter 3.7 --- Conclusion --- p.66 / Chapter 4.0 --- Analysis of plasticisers in foods --- p.67 / Chapter 4.1 --- Introduction --- p.67 / Chapter 4.2 --- Experimental and instrument --- p.67 / Chapter 4.2.1 --- Reagents --- p.68 / Chapter 4.2.2 --- Materials --- p.68 / Chapter 4.3 --- Analysis --- p.69 / Chapter 4.3.1 --- selection of stable isotope labelled analogues --- p.69 / Chapter 4.3.2 --- Synthesis of deuterated internal standard --- p.70 / Chapter 4.4 --- Extraction of foods --- p.71 / Chapter 4.4.1 --- Clean up method --- p.73 / Chapter 4.4.2 --- Quantitation --- p.77 / Chapter 4.5 --- Results and discussion --- p.82 / Chapter 4.5.1 --- Precision test --- p.82 / Chapter 4.5.2 --- Calibration curve --- p.84 / Chapter 4.5.3 --- Detection limit --- p.85 / Chapter 4.5.4 --- Survey of the level of plasticisers in food --- p.86 / Chapter 4.6 --- Conclusion --- p.91 / Chapter 5.0 --- Analysis of plasticisers in food by EI and CI method / Chapter 5.1 --- Introduction --- p.93 / Chapter 5.2 --- Experimental and Instrumental --- p.94 / Chapter 5.2.1 --- Reagents --- p.95 / Chapter 5.2.2 --- Materials --- p.95 / Chapter 5.3 --- Extraction of foods --- p.95 / Chapter 5.3.1 --- Clean up method --- p.95 / Chapter 5.4 --- Result and discussion --- p.95 / Chapter 5.4.1 --- Precision test --- p.95 / Chapter 5.4.2 --- Calibration curve --- p.97 / Chapter 5.4.3 --- Detection limit --- p.99 / Chapter 5.4.4 --- Survey of plasticisers in food by EI and CI method --- p.100 / Chapter 5.4.5 --- Paired t-Test --- p.103 / Chapter 5.5 --- Conclusion --- p.104 / Chapter Chapter 6 --- Conclusion --- p.105 / Bibliography --- p.106 / Appendices : / Chapter 1 --- The mass spectrum of DEP --- p.i / Chapter 2 --- The mass spectrum of DIBA --- p.i / Chapter 3 --- The mass spectrum of DIBP --- p.ii / Chapter 4 --- The mass spectrum of DBP --- p.ii / Chapter 5 --- The mass spectrum of DBS --- p.iii / Chapter 6 --- The mass spectrum of ATBC --- p.iii / Chapter 7 --- The mass spectrum of BBP --- p.iv / Chapter 8 --- The mass spectrum of DEHA --- p.iv / Chapter 9 --- The mass spectrum of DPOP --- p.v / Chapter 10 --- The mass spectrum of DEHP --- p.v / Chapter 11 --- The mass spectrum of DCHP --- p.vi / Chapter 12 --- The mass spectrum of DOAZ --- p.vi / Chapter 13 --- The mass spectrum of DOS --- p.vii / Chapter 14 --- Calibration curve of GC/FID --- p.viii / Chapter 15 --- Calibration curve of GC/MS (magnum) --- p.xi / Chapter 16 --- Calibration curve of GC/MS (GCQ) --- p.xiv

Thesis (Ph. D.)--University of Rhode Island, 2005. / Typescript. Includes bibliographical references (leaves 129-143).

The effects of severely contaminated properties (e.g. NPL sites) on residential property values are well documented. However, most contaminated sites are not so severe to warrant placement on the NPL, and little is known about the impacts to commercial and industrial property markets. Furthermore, perceptions may be developed about different types of land-uses as a result of information made public about sites placed on lists. If perceptions matter, then properties with no known contamination may be viewed as undesirable neighbors in a way similar to listed sites. Therefore, property value impacts could be even more substantial as compared to only the impacts of known contaminated sites. The economic impacts of known and perceived environmental contamination are quantified by estimating two sets of hedonic property value models using data on commercial and industrial property sales for Fulton County, Georgia. Sites listed on the EPA’s CERCLIS and NFRAP reports and the Georgia EPD’s HSI and NonHSI reports are utilized to estimate the impacts of known environmental contamination. The impacts from perceived contamination are estimated utilizing a set of properties that are identified by an ordered probit model that computes the probability commercial and industrial properties may be contaminated. The probability of contamination model is built on factors that are assumed to be key signals to investors in forming their perceptions about the likelihood commercial and industrial properties may be contaminated. Property value losses due to known contamination were estimated at slightly over $1 billion and potential losses from perceived contamination were near $663 million. Although estimated property value impacts are not equivalent to expected gains that may result from the remediation of all contaminated sites, the magnitude of the estimated losses suggests that significant gains can be achieved if property values recover by only a fraction. Policies could be implemented that prioritize site remediation to target minority and/or economically depressed areas to help spur economic development. Potential increases in the tax base would result in greater property tax revenues for the provision of public services for the community and new economic development could help provide access to new jobs for local residents.

Food safety is a critical issue for beef harvest operations. There are multiple interventions available for treating carcasses; however, this project was designed to evaluate an intervention capable of reducing bacterial counts on the hide prior to opening in order to minimize carcass contamination. In Trial I, fresh beef hides (n = 12) were cut into sections and assigned to serve as either clipped (hair trimmed) or non-clipped sections. Sections were inoculated with a bovine fecal slurry and sampled following a water wash. Treatments (distilled water, isopropyl alcohol, 3% hydrogen peroxide, 2% L-lactic acid, 1% cetylpyridinium chloride (CPC), and 10% Povidone-iodine) then were applied to each section and sampled for aerobic plate counts (APCs), coliform, and Escherichia coli counts. Within clipped samples, 1% CPC and 3% hydrogen peroxide caused the greatest reductions in aerobic plate counts, and 1% CPC, 2% L-lactic acid, and 3% hydrogen peroxide showed among the greatest reductions in coliform counts. In Trial II, beef carcasses with hides on were sampled initially and clipped, and then antimicrobials (2% L-lactic acid, 3% hydrogen peroxide, and 1% CPC) were applied before sampling again for APC, coliform, and E. coli counts. This procedure was replicated in Trial II utilizing a non-pathogenic E. coli Type I indicator strain transformed to produce a green fluorescing protein (GFP). In Trial II, though few differences existed between antimicrobial treatments, all three (1% CPC, 2% L-lactic acid, and 3% hydrogen peroxide) resulted in approximately a 2-log10 CFU/100-cm2GFP reduction when applied to clipped hide surfaces in the brisket region of the carcass. In Trial III, 1% CPC produced the greatest reduction on the hide surface for APCs. In Trial IV clipped beef hide sections were sampled initially and then antimicrobials (2% L-lactic acid, 3% hydrogen peroxide, and 1% CPC) were applied before sampling again to determine reduction. Trial IV also involved the use of the E. coli GFP indicator strain. In Trial IV, non-clipped samples had a mean reduction of 2.8 log10 CFU/100 cm2, and clipped samples had a mean reduction of 2.2 log10 CFU/100 cm2. Within the antimicrobials tested, 1% CPC and 3% hydrogen peroxide produced the greatest reductions.

Not available / text

The fluorodinitrobenzene (FONB), succinic anhydride (SA), dansyl chloride (DAN), dye-binding lysine (OBL), total lysine (TL), ninhydrin (NIN) and Tetrahymena lysine (TET) methods were compared for their ability to assess available lysine in soyaprotein heated in the absence or presence of glucose, lactose or xylose and in formaldehyde-treated lactalbumin. The reactive lysine methods showed comparable sensitivity to lysine damage in soyaprotein heated in the absence of sugar, the results indicating the presence of acid labile isopeptides and unidentified acid stable derivatives. Results for soyaprotein heated with glucose, lactose or xylose showed that the type of sugar and the extent of heat treatment has a strong influence on the progress of the Maillard reaction. Furthermore since fructoselysine (F-L) and lactulosyl-lysine (L-L) are colourless up to 30% loss of available lysine can occur without any change in product colour. The FONB method is the most sensitive for mildly damaged glucose-soya samples followed by DAN or OBL, SA and TL whereas for mildly damaged lactose-soya samples the order is OBL, FONB, SA, TL and DAN. For severely damaged samples the DAN or SA methods were the most sensitive followed by OBL, FONB and TL. Formylation of lactalbumin occurred more readily at higher formaldehyde concentrations. Exposure time had less effect while pH (5 and 9) had no effect. Methylene derivatives reached maximum levels sooner than the methylol compounds. Lysine and tyrosine but not histidine formed methylene bridges while tyrosine was found to condense with free formaldehyde during acid hydrolysis raising questions as to the interpretation of similar studies reported in the literature. The FONB, OBL and DAN methods were all very sensitive to this type of damage with the NIN and TL methods being less sensitive and the SA method being completely unsuitable. The TET assay is unsuitable for 'early' Maillard damage since at low sample-N levels growth is stimulated by its ability to utilise unavailable F-L and L-L while at higher N-levels growth is inhibited. No single method is most suitable for all types of damage. Furthermore, all except DAN and DBL are either too long, rather complicated, require expensive equipment or involve the use of dangerous chemicals. The DAN method appears promising but the problem of converting arbitrary fluorescence units to lysine values needs to be overcome. The DBL is recommended for routine analysis since it is simple, economical and highly sensitive to all lysine damage provided care is taken to optimise dye-binding for each type of material analysed. / Thesis (Ph.D.)-University of Natal, Pietermaritzburg, 1985.

This thesis investigated the dissolution of dense non aqueous phase liquids (DNAPL) source zones in the subsurface and the effectiveness of enhanced bioremediation for the treatment of chlorinated ethene DNAPLs, using numerical modeling. For this purpose, an existing multiphase numerical model was extended to include comprehensive models for the processes of dissolution and reaction. The first part of the thesis examined DNAPL dissolution. First, a thermodynamic-based dissolution model was validated using experimental data from two complex heterogeneous DNAPL releases. Model predictions for DNAPL spatial distribution and effluent concentrations agreed well with experimental measurements, without requiring calibration. This is the first successful application of a predictive dissolution model in the literature. Model results showed the important effects of relative permeability and interfacial areas on dissolution rates. Then, the thermodynamic dissolution model was compared to simpler models typically used in the literature. Five Sherwood-Gilland (SG) empirical correlations were evaluated and their limitations were illustrated. A new dissolution model was proposed that combined the predictive ability of the thermodynamic model and the simplicity of SG models, and is applicable for complex source zones. Lastly, the relationship between the DNAPL source architecture and downstream concentrations was investigated, focusing on multistage concentration profiles. A new upscaled model was proposed that is able to capture such complex behavior. In the second part of this thesis the thermodynamic dissolution model was combined with a model for reductive dechlorination of chlorinated ethenes to simulate DNAPL bioremediation. Simulations were conducted for simple DNAPL source zones to investigate the impact of dissolution-related processes on bioremediation effectiveness. Dissolution kinetics and back-partitioning of daughter products in the DNAPL were shown to affect dechlorination. Then, the investigation was extended to DNAPL source zones of complex architectures in heterogeneous domains, illustrating the importance of the source zone architecture for the effectiveness of DNAPL bioremediation. Overall, this thesis presents a comprehensive numerical model that will be an important research tool for evaluating the effectiveness of in-situ bioremediation for DNAPL source zones, and will provide the means for a better understanding and control of the critical factors affecting this technology in the field.

This thesis investigated the dissolution of dense non aqueous phase liquids (DNAPL) source zones in the subsurface and the effectiveness of enhanced bioremediation for the treatment of chlorinated ethene DNAPLs, using numerical modeling. For this purpose, an existing multiphase numerical model was extended to include comprehensive models for the processes of dissolution and reaction. The first part of the thesis examined DNAPL dissolution. First, a thermodynamic-based dissolution model was validated using experimental data from two complex heterogeneous DNAPL releases. Model predictions for DNAPL spatial distribution and effluent concentrations agreed well with experimental measurements, without requiring calibration. This is the first successful application of a predictive dissolution model in the literature. Model results showed the important effects of relative permeability and interfacial areas on dissolution rates. Then, the thermodynamic dissolution model was compared to simpler models typically used in the literature. Five Sherwood-Gilland (SG) empirical correlations were evaluated and their limitations were illustrated. A new dissolution model was proposed that combined the predictive ability of the thermodynamic model and the simplicity of SG models, and is applicable for complex source zones. Lastly, the relationship between the DNAPL source architecture and downstream concentrations was investigated, focusing on multistage concentration profiles. A new upscaled model was proposed that is able to capture such complex behavior. In the second part of this thesis the thermodynamic dissolution model was combined with a model for reductive dechlorination of chlorinated ethenes to simulate DNAPL bioremediation. Simulations were conducted for simple DNAPL source zones to investigate the impact of dissolution-related processes on bioremediation effectiveness. Dissolution kinetics and back-partitioning of daughter products in the DNAPL were shown to affect dechlorination. Then, the investigation was extended to DNAPL source zones of complex architectures in heterogeneous domains, illustrating the importance of the source zone architecture for the effectiveness of DNAPL bioremediation. Overall, this thesis presents a comprehensive numerical model that will be an important research tool for evaluating the effectiveness of in-situ bioremediation for DNAPL source zones, and will provide the means for a better understanding and control of the critical factors affecting this technology in the field.

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