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Drug vehicles are chemical carriers that aid a drug's passage through an organism. Whilst they possess no intrinsic efficacy they are designed to achieve desirable characteristics which can include improving a drug's permeability and or solubility, targeting a drug to a specific site or reducing a drug's toxicity. All of which are ideally achieved without compromising the efficacy of the drug. Whilst the majority of drug vehicle research is focused on the solubility and permeability issues of a drug, significant progress has been made on using vehicles for toxicity reduction. Achieving this can enable safer and more effective use of a potent drug against diseases such as cancer. From a molecular perspective, drugs activate or deactivate biochemical pathways through interactions with cellular macromolecules resulting in toxicity. For newly developed drugs such pathways are not always clearly understood but toxicity endpoints are still required as part of a drug's registration. An understanding of which vehicles could be used to ameliorate the unwanted toxicities of newly developed drugs would be highly desirable to the pharmaceutical industry. In this paper we demonstrate the use of different classifiers as a means to select vehicles best suited to avert a drug's toxic effects when no other information about a drug's characteristics is known. Through analysis of data acquired from the Developmental Therapeutics Program (DTP) we are able to establish a link between a drug's toxicity and vehicle used. We demonstrate that classification and selection of the appropriate vehicle can be made based on the similarity of drug choice.

Biogas slurry has become a serious pollution problem and anaerobic digestion is widely applied to pig manure treatment for environmental protection and energy recovery. To evaluate environmental risk of the emission of biogas slurry, luminescent bacteria (Vibrio fischeri), larvae and embryos of zebrafish (Danio rerio) were used to detect the acute and development toxicity of digested and post-treated slurry. Then the ability of treatment process was evaluated. The results showed that digested slurry displayed strong toxicity to both zebrafish and luminescent bacteria, while the EC50 for luminescent bacteria and the LC50 for larvae were only 6.81% (v/v) and 1.95% (v/v) respectively, and embryonic development was inhibited at just 1% (v/v). Slurry still maintained a high level of toxicity although it had been treated by membrane bioreactor (MBR), while the LC50 of larvae was 75.23% (v/v) and there was a little effect on the development of embryos and V. fischeri, the results also revealed that the zebrafish larvae are more sensitive than embryos and luminescent bacteria to pig slurry. Finally, we also found the toxicity removal rate was higher than 90% after the treatment of MBR according to toxicity tests. In conclusion, further treatment should be used in pig slurry disposal or reused of final effluent.

This work evaluated the toxicity reduction of abamectin in an aqueous solution (500 μg L

Inorganic nutrients were applied to oiled wetland sediments during an experiment to assess the effect of enhanced bioremediation on petroleum degradation and toxicity reduction. For a period of 6 months after the controlled application of oil to experimental plots, oiled wetland sediment samples were tested for acute toxicity. The three treatments evaluated were an oiled control, inorganic nutrient addition, and inorganic nutrient addition plus an alternate electron acceptor. Sediment toxicity was assessed using Microtox® and amphipod bioassays. The Microtox® 100% Test detected significant sediment toxicity up to 29 days after oil and treatment application while the Solid-Phase Test detected significant sediment toxicity up to Day 15. The Microtox 100%® Test showed elevated toxicity on Day 8 for nutrient plus alternate electron acceptor plots and reduced toxicity on Day 15 for nutrient plots, relative to oiled controls. The observed decrease in sediment toxicity from the Microtox® assays correlated with petroleum losses. Oiled sediments were initially highly toxic to amphipods with average mortality rates ranging from 86 to 92%. Amphipod mortality decreased significantly 71 days after treatment to between 47 and 28%. However, a significant increase in mortality was observed at Day 140 in plots receiving nutrient amendments, possibly due to elevated ammonia levels.

Reservoirs situated along a river continuum are ecosystems where rates of transfer of suspended matter and associated micropollutants are reduced due to sedimentation, accumulation, and biological and physical transformation processes. Among the micropollutants, PCDDs and PCDFs are substances that are highly toxic and carcinogenic for humans and animals. They are emitted and dispersed in the environment throughout the whole catchment area and may accumulate in aquatic and terrestrial food chains, creating a risk for human health. A wealth of data exists indicating the increase in the concentrations of pollutants along a river continuum. A comparative analysis of total, individual, and TEQ PCDD/PCDF concentrations in large lowland, shallow reservoirs located in different catchments (“I”—industrial/urban/ agricultural, “U”—urban/agricultural, and “A”—agricultural/ rural) showed decreases of the TEQ concentrations in bottom sediments along a gradient from the middle sections to the dam walls. Moreover, penta-, hexa-, and heptachlorinated CDD/CDF congeners were reduced from 28.8 up to 93.6 % in all three types of reservoirs. A further analysis of water samples from the inlets and outlets of the “A” reservoir confirmed this tendency. The authors wish to express their sincere appreciation to Prof. Konrad Rydzyński from the Nofer Institute of Occupational Medicine in Lodz, Prof. Richard Robarts from the UNEP Global Environment Monitoring System (GEMS)/Water Programme, Prof. Paul DuBowy from the U.S. Army Corps of Engineers, and Prof. David Harper from the Department of Biology, the University of Leicester for their constructive comments on an earlier version of this paper. The authors also wish to acknowledge the research team of the Nofer Institute of Occupational Medicine in Lodz: Dr Danuta Ligocka and Dr Wiktor Wesołowski for their assistance during the laboratory processes. The research was supported by the following projects of the Polish Ministry of Science and Higher Education: – N N305 365738 “Analysis of point sources pollution of nutrients, dioxins and dioxin-like compounds in the Pilica River catchment and draw up of reclamation methods”; – 2PO4 G08830 “Accumulation of dioxins and dioxin-like pollutants in the food chain of the Sulejowski and Włocławski Reservoirs: chemometric analysis and toxicological estimation”.

Background An eco-friendly treatment of industrial effluents is a major environmental concern of the modern world in the face of stringent environmental legislations. By keeping in mind the extensive industrial applications of ligninolytic enzymes, this study was performed to purify, and immobilize the manganese peroxidase (MnP) produced from an indigenous strain of Ganoderma lucidum. The present study was also focused on investigating the capability of immobilized MnP for decolorization of dye containing textile effluents. Results A large magnitude of an indigenous MnP (882±13.3 U/mL) was obtained from white rot fungal strain G. lucidum in solid state bio-processing of wheat straw under optimized fermentation conditions (moisture, 50%; substrate, 5 g; pH, 5.5; temperature, 30°C; carbon source, 2% fructose; nitrogen source, 0.02% yeast extract; C: N ratio, 25:1; fungal spore suspension, 5 mL and fermentation time period, 4 days). After ammonium sulfate fractionation and Sephadex-G-100 gel filtration chromatography, MnP was 4.7-fold purified with specific activity of 892.9 U/mg. G. lucidum MnP was monomeric protein as evident by single band corresponding to 48 kDa on native and denaturing SDS-PAGE. The purified MnP (2 mg/mL) was immobilized using a sol–gel matrix of tetramethoxysilane (TMOS) and proplytrimethoxysilane (PTMS). The oxidation of MnSO4 for up to 10 uninterrupted cycles demonstrated the stability and reusability of the immobilized MnP. Shelf life profile revealed that enzyme may be stored for up to 60 days at 25°C without losing much of its activity. To explore the industrial applicability of MnP produced by G. lucidum, the immobilized MnP was tested against different textile effluents. After 4 h reaction time, the industrial effluents were decolorized to different extents (with a maximum of 99.2%). The maximally decolorized effluent was analyzed for formaldehyde and nitroamines and results showed that the toxicity parameters were below the permissible limits. Conclusions In conclusion, G. lucidum MnP was immobilized by sol–gel matrix entrapment with an objective to enhance its practical efficiencies. The MnP was successfully entrapped into a sol- gel matrix of TMOS and PTMS with an overall immobilization efficiency of 93.7%. The sol- gel entrapped MnP seems to have prospective capabilities which can be useful for industrial purposes, especially for bioremediation of industrial effluents.

Recent technological advances in nanotechnology, molecular biology, and imaging technology allow the application of nanomaterials for early and specific cancer detection and therapy. As early detection is a prerequisite for successful treatment, this area of research has been rapidly growing. This paper provides an overview of recent advances in production, functionalization, toxicity reduction, and application of nanoparticles to cancer diagnosis, treatment, and treatment monitoring. This review focuses on superparamagnetic nanoparticles used as targeted contrast agents in MRI, but it also describes nanoparticles applied as contrasts in CT and PET. A very recent development of core/shell nanoparticles that promises to provide positive contrast in MRI of cancer is provided. The authors concluded that despite unenviable obstacles, the progress in the area will lead to rapidly approaching applications of nanotechnology to medicine enabling patient-specific diagnosis and treatment.

Identification of what is “toxic” in aquatic toxicity tests is most often determined quantitatively through the regulatory process as permit limits or objectives and no definitive standards have been defined or are universally used. Although no universal definitions exist, several measures of toxicity are more commonly employed and seem to have achieved greater acceptance. These include the use of the “no observed effect concentration” (NOEC) or “no observed effect level” (NOEL). The NOEC and NOEL use hypothesis testing to identify statistically significant differences relative to a nontoxic control. The NOEC or NOEL is defined as the highest concentration not significantly different from the control. Another commonly used analysis involves various point estimation techniques. These quantitative analyses use dose–response data to estimate “safe” or “nontoxic” concentrations or effects using metrics such as the LC50 (lethal concentration causing a 50% effect) or EC/IC25 (effective or inhibition concentration causing a 25% effect). Due to the large amount of toxicity testing required in the TIE process, reductions in testing replication and exposure volume and duration are often made to save on sample and staffing resources. Keywords: toxicity; toxicity identification evaluation TIE; toxicity reduction evaluation TRE

Chlorophenols are well-known priority pollutants and many different treatments have been assessed to facilitate their removal from industrial wastewater. However, an absolute and optimum solution still has to be practically implemented in an industrial setting. In this work, a series ofphysical, chemical and biochemical treatments have been systematically tested for the removal of 4-chlorophenol, and their results have been compared in order to determine the most effective treatment based on removal efficiency and residual by-product formation. Chemical treatments based on advanced oxidation processes (AOP) produced the best results on rate and extent of pollutant removal. The non-chemical technologies showed advantages in terms of complete (in the case of adsorption) or easy (enzymatic treatments) removal of toxic treatment by-products. The AOP methods led to the production of different photoproducts depending on the chosen treatment. Toxic products remained in most cases following treatment, though the toxicity level is significantly reduced with combination treatments. Among the treatments, a photochemical method combining UV, produced with a KrCl excilamp, and hydrogen peroxide achieved total removal of chlorophenol and all by-products and is considered the best treatment for chlorophenol removal.

The influence of processing variables: mixing time, waste/binder ratio and water/ solid ratio on the solidification/stabilization process of steel foundry dust has been studied. The characterization of the final product was based on the Toxic Characterization Leaching Procedure (TCLP) followed by the biotoxicity (bioluminescence assay) and concentration of the metals, Cr, Cd, Pb and Zn in the leachates. The final product characteristics depend mainly on the waste/binder ratio, as a function of the metal hydroxide solubilities. The results of this work allow one to establish the optimization of a solidification/stabilization process for steel foundry dust.

A laboratory scale activated sludge treatment system was developed for the treatment of phenoxy herbicide chemicals and the associated chlorophenols in a toxic landfill leachate. A novel sludge recycle system was employed to ensure high specific activity of the return sludge. The activated sludge treatment resulted in 99.5% removal of phenoxies and chlorophenols and 84% TOC reduction for 10% influent leachate concentrations. The corresponding toxicity reduction was 76%. An increase in influent concentration resulted in a decline in activated sludge performance.

In the present article, the efficiency of biological treatment of landfill leachates was evaluated by implementation of physicochemical characterisation and a complex toxicity assessment. An array of toxicity tests using bacterium Vibrio fischeri, alga Desmodesmus subspicatus, crustacean Daphnia magna, and embryo of fish Danio rerio, as well as unconventional methods using biochemical biomarkers (protein content, enzymes cholinesterase, and glutathione-S-transferase), were employed. Toxicity of leachates varied depending on the season of collection in relation to their different physicochemical characteristics. Uncommon effects of leachates on organisms, such as hormetic-like increases of algal growth and reproduction of daphnids, were identified. New approaches using the activities of enzymes were found unsuitable for routine hazard assessment of leachates. Although physicochemical parameters and toxicity decreased significantly after biological treatment, the effluents did not meet the demands of the current Slovenian legislation; thus, the existing biological treatment was found inappropriate. The development of advanced treatment techniques for landfill leachates is thus encouraged.

The photo processing industry can be characterized by treatment processes and subsequent silver recovery. The effluents generated all contain various amounts of silver. The objectives of this study were to determine toxicity of photo processing effluents and to explore their toxicity mitigation. Six samples, from small shops to a major photo processing center, were studied. Two samples (I and VI) were found to be extremely toxic, causing 100 and 99% inhibition of duckweed frond reproduction, respectively, and were used for subsequent toxicity reduction experiments. Lime and sodium sulfide were effective for the toxicity reduction of Sample VI; both reduced its toxicity to negligible. Sample I was far more toxic and was first diluted to 2.2% and then treated with 0.5 g lime/100 mL, reducing toxicity from 100% to 12% inhibition.

A toxicity characterization protocol has been developed which incorporates many of the effluent fractionation techniques described in other procedural manuals and papers. The objective of this protocol is not only to determine the categorical source of toxicity, but also to provide an insight as to the appropriate treatment(s) which will result in toxicity reduction. This protocol has been applied to a variety of freshwater and saltwater municipal and industrial effluents. These applications have tested both fish and invertebrates and have been used to assess acute as well as chronic toxicity. The results of several studies are provided and discussed as to their success in identifying the toxic component(s) and/or providing a treatment option to alleviate the toxicity problem. A review of the limitations and precautions associated with these procedures and with data interpretation is also presented.

PURPOSE OF REVIEW: To review the use of measurement tools for reporting gastrointestinal toxicity in radiation oncology to highlight recent findings of potential interest to those involved in the treatment of tumors in the pelvis, assessment of survivorship issues or management of bowel effects. RECENT FINDINGS: Multiple measurement tools are being used in radiation oncology studies involving both clinician and patient-reported outcomes. The increasing availability of accurate data on radiation doses and dose-volumes to normal tissues is enabling identification of critical areas where dose should be reduced to minimize organ damage. SUMMARY: Measurement tools for gastrointestinal symptoms are important to highlight therapeutic benefit for the expanding investigations of treatment intensification approaches and methods for toxicity reduction. The increasing use of the CTCAEv3 scales is a step forward, but further research is required to refine the system and improve its ease of use within routine clinical practice.

In response to proposed Zn limits for the NPDES outfall H-12, a Zn screening Water Effects Ratio (WER) study was conducted to determine if a full site-specific WER is warranted. Using standard assumptions for relating the lab results to the stream, the screening WER data were consistent with the proposed Zn limit and suggest that a full WER would result in a similar limit. Addition of a humate amendment to the outfall water reduced Zn toxicity, but the toxicity reduction was relatively small and unlikely to impact proposed Zn limits. The screening WER data indicated that the time and expense required to perform a full WER for Zn is not warranted.

The sludge wastes generated by the metal plating industries are classified as hazardous wastes because of their high concentration of heavy metals. Amongst the various routes for their treatment, the hydrometallurgical processes are highly attractive because they can be tailored to the wide compositional range of such wastes and assure its metals recovery and/or toxicity reduction. In these processes the leaching operation is paramount to the overall efficiency. In this, the mixing of the leaching solution with sludge has to be effective in order to obtain high levels of metal extraction and make the process attractive. Most of the available data refers to laboratory tests. This paper reports on the use of CFD model to optimize the operation of a pilot size leaching tank. The results regarding the velocity field were compared with experimental data and proved that such techniques can be effectively applied to improve the process. A leaching experiment, with the best configuration for the mixing, yielded a high metal extraction, suggesting that this technique can be successfully implemented for the treatment of such wastes.Copyright © 2009 by ASME

Recent legislation in the United States is placing emphasis on the removal of priority pollutants and aquatic toxicity from industrial wastewaters. A protocol has been developed to select candidate technologies for specific effluent objectives. Design parameters for biological treatment are developed using a modified FBR test. The applicability of alternative physical-chemical technologies are discussed.

In order to improve the effluent from domestic sewage treatment through an anaerobic process in an upflow anaerobic sludge blanket reactor (UASB), CETESB - The Environmental Protection Agency for Sao Paulo State, and FILSAN - Equipamentos e Sistemas S/A, developed a joint program to study the effectiveness of ozonation of the effluent as a post-treatment process. As the effluents treated by this system could contain toxic chemicals, Daphnia similis toxicity tests were applied. Two ozonation conditions were evaluated: (1) contact time of 30 min, mean ozone application dosage of 15.9 mg/L; (2) contact time of 50 min, mean ozone application of 16.7 mg/L. Toxicity reduction occurred for all samples but one. The ozonation system eliminated the residual toxicity associated with the effluent treated by the UASB reactor.

An atrazine photodegradation study carried out by a Q-Panel suntest apparatus is reported in this work. H 2 O 2 /TiO 2 photocatalyzed reaction yield and parameters (time, irradiance, temperature, H 2 O 2 (40%) volume, TiO 2 amount) were exactly determined relating to the used atrazine concentration. An experimental kinetic study was performed to establish the reaction order in fixed conditions. Using a biosensor method, 10 -4 M Atrazine solution toxicity and final photocatalytic reaction solution toxicity were quantitatively determined. A consistent toxicity decrease was observed on passing from the analyte to the products of the photocatalytic reaction. An analogous photolytic reaction carried out in absence of TiO 2 , but in the same experimental conditions of time, irradiance, temperature and H 2 O 2 volume, brings to a toxicity increase.

The Toxicity Reduction Evaluation process is a logical site-specific set of procedures which can be used for preventing and resolving toxicity with a variety of aqueous media, including industrial and municipal effluent, receiving water (surface water), groundwater, leachates and sediment porewater. Factors influencing success of a TRE include establishing a Toxicity Prevention/Response Plan prior to the initial toxicity episode, experience and knowledge of the investigators, inclusion of a multi-disciplinary team, effective mechanisms for communication and co-ordination among all stakeholders, and flexibility in site-specific studies. The methods for the prevention and reduction of toxicity are not limited to the guidance provided in the preceding sections. Significant new and useful advances in toxicant identification are made on a regular basis; as these methods or approaches are developed, they should be included for consideration as part of the TRE.

Textile effluent is discharged to sewer with little or no destructive treatment. In investigating the effects of sewage treatment on textile effluent we aim to establish the biodegradability of the effluent and the reduction in toxicity exerted on aquatic organisms resulting from standard sewage treatment. Using three separate samples of effluent, the initial toxicity was tested using the aquatic invertebrate Daphnia magna. The samples were biodegraded following the Zahn-Wellens method and then retested. Results showed relatively good biodegradability but negligible toxicity reduction. The ‘hard COD’, or non-degradable, portion of the effluent, which appears to be responsible for exerting toxicity, is not altered by this treatment method.

Trabalho completo: acesso restrito, p. 1277–1281 Submitted by Bruna Lessa (lessbruna@gmail.com) on 2012-08-13T20:01:02Z No. of bitstreams: 1 (158).pdf: 178846 bytes, checksum: 428c76254625e51ed06f6e4880481d9f (MD5) Made available in DSpace on 2012-08-13T20:01:02Z (GMT). No. of bitstreams: 1 (158).pdf: 178846 bytes, checksum: 428c76254625e51ed06f6e4880481d9f (MD5) Previous issue date: 2005-03 The treatment efficiency, as toxicity removal, of complex effluents from the Industrial District of Camaçari (BA, Brazil), after biological treatment with activated sludge was evaluated using Microtox®. Samples of the equalised effluent (EE) were collected prior to treatment together with samples of the treated effluent (TE), which remained 24 h in the treatment plant. Rehydrated colonies of Vibrio fischeri were exposed to sequential dilutions of EE and TE to assess luminosity interference. Values for EC50 were calculated, together with the respective toxicity units. In all, twenty assays of each effluent type were carried out and the mean toxicity removal was 92.71%, while the chemical oxygen demand (COD) presented mean reduction of 83.04%. There was a variability of an order of magnitude between the Microtox® results for the two types of effluents. The mean EC50 values were 2.12 for EE and 47.78% for TE. In spite of its weakness in some conditions, the Microtox® system demonstrated to work adequately in assessing effluent toxicity removal in this treatment plant and therefore can be used for further toxicity removal programs.

The Data Quality Objective Procedure (DQOP) method aids implementing environmental polices, as engineering solutions. Pollution control issues identified and addressed through new environmental legislation need to be implemented. The metal matrix encapsulation (MME) treatment works as a toxicity reduction exercise that can legally control disposal of fly ashes from waste-to-energy plants. The MME process aids with the implementation of European Union (EU) legislation such as the Waste Incineration Directive by allowing fly ashes to be disposed of in landfill sites. By using the DQOP, as shown with the MME fly ash treatment, complex issues can be clearly identified and effectively controlled. The method considers various steps into which different activities can be addressed, agreed upon and allows engineering, financial and legal teams to cooperate. The EU is the world’s second largest economy with many waste management requirements. The DQOP can aid entry into this complex but rich economic opportunity.Copyright © 2005 by ASME

Degradability of four textile dyes was investigated in deionized water solutions during 520 kHz ultrasonic irradiation. It was found that for all dyes, the rate of color decay was first order in the visible absorption of the dye, and related to the type of functional groups that characterized the chromophore in the dye molecules. The destruction of aromatic/olefinic carbons in azo dyes was slower than that of color––to be attributed to the priority of hydroxyl radical attack on the NN bonds, and to the formation of numerous oxidation intermediates of organic character during the course of dye degradation. Toxicity analysis of the dye solutions prior to sonolysis revealed that “reactive” dyes were non-toxic, but “basic” ones were toxic at the test concentrations employed in the study. Significant degrees of toxicity reduction were accomplished along with color and aromatic carbon degradation.

The potential of IMRT to reduce toxicity was investigated. Initially, a treatment plan was set-up on the CORVUS1 inverse treatment planning system using nine equi-spaced beams. The goal of the inverse plan was to reduce the dose to the cochlea and the oral cavity compared to the conformal wedged pair technique. The plan reduced the dose to the cochlea and to a lesser extent reduced the volume of the oral cavity receiving high-dose, and also improved the PTV homogeneity. Unfortunately, compared to the conformal wedged pair technique, the IMRT plan greatly increased the dose to the contralateral parotid gland with 73% of the OAR receiving dose in excess of 6 Gy.

[Formulae and special characters can only be approximated here. Please see the pdf version of the Abstract for an accurate reproduction.] Several inert platinum complexes were synthesised: [(en)Pt([special character]-dpzm)2Pt(en)]4+, [{Pt(dien)}2[special character]-dpzm]4+, [{Pt(dien)}2[special character]-H2N-(CH2)6-NH2]4+, cis-[(NH3)2Pt([special character]--dpzm)2Pt(NH3)2]4+, trans-[Pt(NH3)2([special character]-dpzm)2]2+. Three active complexes, all with chloro ligands, were also synthesised: trans-[{Pt(NH3)Cl2}2[special character]-dpzm)], trans-[{Pt(NH3)2Cl}2[special character]-dpzm]2+ (di-Pt) and trans-[trans-{Pt(NH3)2Cl}2{trans-[Pt(NH3)2([special character]-dpzm)2]}]4+ (tri-Pt). 1H NMR established that multi-nuclear platinum complexes will preferentially associate in the DNA minor groove with a preference for A/T sequences, and with a binding constant [special character]-105 M-1, regardless of the charge, linking ligand, length or shape. Using [(en)Pt([special character]-dpzm)2Pt(en)]4+ and the oligonucleotide d(GC)5 it was determined that the metal complex binds G/C rich sequences also in the minor groove, but with a much reduced binding constant, 103 M-1. CD studies showed [(en)Pt([special character]-dpzm)2Pt(en)]4+ was able to induce a DNA conformation change from B-type to what appeared to be a partial Z-type. Transcription assays showed that even though the metal complex does not bind DNA covalently, it is still able to inhibit DNA transcription at particular sites. The complexes di-Pt, tri-Pt, [{Pt(dien)}2[special character]-dpzm]4+ and trans-[Pt(NH3)2([special character]-dpzm)2]2+ were tested for anti-cancer activity in the L1210 murine leukaemia cell line, and gave values of 3.8, 2.5, [special character]200 and 64 [special character]M respectively. In the cisplatin resistant line (L1210/DDP), trans-[Pt(NH3)2([special character]-dpzm)2]2+ showed an increase in activity with a drop to 32 [special character]M, while both di-Pt and tri-Pt showed decreases in activity to values of 8.8 and 3.6 [special character]M. In the human ovarian carcinoma 2008 cell line and its cisplatin resistant derivative C13[special character]5, both complexes showed good activity with values of 2.5 and 20.9 [special character]M respectively, but again both showed decreases in activity in the resistant line with values of 17.8 and 37.7 [special character]M respectively. To help explain the difference between activity of these complexes and the complexes BBR3464 and BBR3005, cell uptake and DNA interstrand cross-linking experiments were performed. The cell uptake studies showed that both di-Pt and tri-Pt are taken up by cells at very high levels, when administered at 100 [special character]M, thus indicating that the difference is unlikely to be due to large differences in cell uptake. The DNA interstrand cross-linking studies showed both complexes readily form interstrand adducts (50% interstrand cross-linking at 12 nM and 22 nM respectively, c.f cisplatin 3 [special character]M). These results suggest that the rigid nature of the dpzm linker may be affecting the DNA adducts formed, with more interstrand links being formed than BBR3464. Possibly, it is this that causes the large differences in cytotoxicity. The DNA binding of di-Pt and tri-Pt was examined with the nucleosides adenosine and guanosine and the dinucleotide d(GpG). Both complexes bound at the N7 of guanosine, but 2-fold slower than cisplatin. In addition, di-Pt bound at the N7 and either the N1 or N3 of adenosine, 7-fold slower than guanosine. Di-Pt forms a large variety of cross-links between two d(GpG) molecules, however it could not be established whether the 1,2-intrastrand adduct could be formed. Di-Pt, however, forms a 1,2-GG interstrand adduct with the oligonucleotide d(ATGCAT)2 resulting in a conformation change away from B-type DNA. The sugar pucker of the G3 nucleoside changes from 2[special character]-endo towards 3[special character]-endo, and the position of the nucleotide relative to the sugar changes from anti to syn. The ability of multi-nuclear platinum complexes to form covalent adducts in the DNA minor groove remains unclear. It appears that di-Pt can form up to 33% minor groove adducts with the oligonucleotide d(AT)5, but when added to the oligonucleotide d(GCCAAATTTCCG)2 no definite minor groove adducts are seen and the major adduct appears to be a 1,2-interstrand cross-link between the two A6's or between the G1 and G11. Finally, a study of the encapsulation of platinum complexes within cucurbit[7]uril (Q7) as a means of reducing drug toxicity was made. For complex A and di-Pt, encapsulation of the linker ligand occurred. The effect of Q7 on the rate of hydrolysis of di-Pt was at least a 3-fold reduction as compared to free di-Pt with guanosine. Studies with [{Pt(dien)}2[special character]-dpzm]4+/Q7 and the oligonucleotide d(CGCGAATTCGCG)2 showed that the metal complex could dissociate from the Q7 and associate with the oligonucleotide, where an equilibrium is achieved with 15 % of the metal complex bound to the oligonucleotide and 75 % encapsulated in Q7. Tests in the L1210 and L1210/DDP cancer cell lines showed that di-Pt/Q7 has almost the same activity compared to free di-Pt.

Several committees were established by the National Association of Physicians for the Environment to investigate and report on various topics at the National Leadership Conference on Biomedical Research and the Environment held at the 1--2 November 1999 at the National Institutes of Health in Bethesda, Maryland. This is the report of the Committee on Minimization and Management of Wastes from Biomedical Research. Biomedical research facilities contribute a small fraction of the total amount of wastes generated in the United States, and the rate of generation appears to be decreasing. Significant reductions in generation of hazardous, radioactive, and mixed wastes have recently been reported, even at facilities with rapidly expanding research programs. Changes in the focus of research, improvements in laboratory techniques, and greater emphasis on waste minimization (volume and toxicity reduction) explain the declining trend in generation. The potential for uncontrolled releases of wastes from biomedical research facilities and adverse impacts on the general environment from these wastes appears to be low. Wastes are subject to numerous regulatory requirements and are contained and managed in a manner protective of the environment. Most biohazardous agents, chemicals, and radionuclides that find significant use in research are not likely to be persistent, bioaccumulative, or toxic if they are released. Today, the primary motivations for the ongoing efforts by facilities to improve minimization and management of wastes are regulatory compliance and avoidance of the high disposal costs and liabilities associated with generation of regulated wastes. The committee concluded that there was no evidence suggesting that the anticipated increases in biomedical research will significantly increase generation of hazardous wastes or have adverse impacts on the general environment. This conclusion assumes the positive, countervailing trends of enhanced pollution prevention efforts by facilities and reductions in waste generation resulting from improvements in research methods will continue.

Purpose: To reduce the overall treatment fractions by about a week and minimize the skindose toxicity by treating stage I‐II breast cancer patients with IMRT and eventually RapidArc both, incorporating a simultaneous boost to the tumor bed. Background:Radiation therapy is prescribed to breast cancer patients after receiving a lumpectomy or mastectomy to remove canceroustissue. In the past, treatments using two 6MV tangential fields with wedges followed by an electron boost to the tumor bed have often resulted in unnecessary dose to unaffected tissue. As a consequence, patients experienced edema, pain, desquamation, discoloration, and other negative side‐effects. IMRT and RapidArc are treatment techniques where the dose can be tailored to the shape of the target, reducing the exposure of adjacent tissues to unnecessary radiation and potential damage. Methods and Materials:Skindose measurements using TLDs from 35 patients receiving conventional radiotherapy were collected over a period of 9 months. Seven 3×3×1 mm3TLD chips were placed on the 4 quadrants of a patient's breast and 3 on the inframmary fold. Same TLD arrangement was used for patients receiving IMRT or RapidArc which, in addition, incorporated a simultaneous boost of an additional ∼10Gy delivered to the tumor bed, within the regular 28 treatment sessions. Results: Preliminary data indicates percent differences of 4–20% less skindose on the IMRT/RapidArc cases, primarily in the inframammary fold region. Furthermore, our skindose data on the IMRT/RapidArc treatments indicates a strong correlation to the size and shape of the breast under treatment suggesting that patients with large breast may experience little skin sparing — confirming observations reported elsewhere. Dose to heart, lungs and contralateral breast were kept to a minimum. Conclusion: This work continues with more breast patients receiving IMRT or RapidArc, and thus far the data continues to support our preliminary observations.

The treatment of textile dyeing and finishing wastewaters by conventional methods, such as biological, physical and chemical processes or combinations thereof, are in common practice but have unique drawbacks, namely, a number of refractory chemicals in the effluents and difficulty in the complete removal of color. The study described herein is an investigation of an advanced oxidation treatment of a common azo dye, Remazol Black-B, widely used in textile dyeing and finishing operations. The investigation was focused on monitoring the degradation and toxicity reduction of an aqueous solution of the dye up to 30 min of treatment by a UV/H

Aims: The purpose of this study was to evaluate the performance of the sequential application of ozonation and activated carbon processes in the elimination of water-soluble crude oil and thereby reducing total organic carbon (TOC) and toxicity for the rainbow trout larvae. Materials and Methods: A series of water-soluble fractions of crude oil, 5-100 ml/l, were prepared. Groups of ten rainbow trout fish larvae were exposed to the solution for 24, 48, and 96 hours. Toxicity (LC 50 : Median lethal concentration) and TOC tests were performed for the solutions before and after their treatment by sequential ozonation and activated carbon adsorption. Results: The LC 50 (96 hours) and TOC of the sample before the treatment process were 60 mg/l and 55 mg/l, respectively. After adsorption by 10 mg/l activated carbon, followed by ozonation with a concentration of 1 mg/l, the LC 50 increased to 145 mg/l and TOC reduced to 36 mg/l. Those values, after treatment with 30 mg/l activated carbon, followed by 7 mg/l ozone, reached 196 mg/l and 28 mg/l, respectively. In the experiment, ozonation by 1 mg/l ozone was applied, and then adsorption was carried out by 10 mg/l activated carbon, and the LC 50 was 149 and TOC was 35 mg/l. In the experiments with 7 mg/l ozone followed by 30 mg/l activated carbon, LC 50 reached 204 mg/l and TOC reduced to 28.5 mg/l. Conclusions: Primarily ozonation of crude oil polluted waters followed by adsorption by activated carbon can increase the removal efficiency of the process, which results in significant TOC and toxicity reduction.

Applications using microwave energy in the chemical processing industry have increased within the last ten years. Recently, interest in waste treatment applications process development, especially solidification, has grown. Microwave waste processing offers many advantages over conventional waste treatment technologies. These advantages include a high density, leach resistant, robust waste form, volume and toxicity reduction, favorable economics, in-container treatment, good public acceptance, isolated equipment, and instantaneous energy control. The results from the {open_quotes}cold{close_quotes} demonstration scale testing at the Rocky Flats nuclear weapons facility are described. Preliminary results for a transuranic (TRU) precipitation sludge indicate that volume reductions of over 80% are achievable over the current immobilization process. An economic evaluation performed demonstrated cost savings of $11.68 per pound compared to the immobilization process currently in use on wet sludge.

Complex mixtures of chemicals, many defined as hazardous and toxic, increasingly enter surface soils through spills and unregulated land disposal. The regulatory and technical challenge is to use cost-effective control technologies that can treat complex chemical mixtures in contaminated soils and thereby reduce the resultant threat to human health and the environment. Bioremediation can be such a technology.