National Library of Energy BETA

Sample records for highly toxic herbicides

  1. Mechanisms of olfactory toxicity of the herbicide 2,6-dichlorobenzonitrile: Essential roles of CYP2A5 and target-tissue metabolic activation

    SciTech Connect (OSTI)

    Xie Fang; Zhou Xin; Behr, Melissa; Fang Cheng; Horii, Yuichi; Gu Jun; Kannan, Kurunthachalam; Ding Xinxin

    2010-11-15

    The herbicide 2,6-dichlorobenzonitril (DCBN) is a potent and tissue-specific toxicant to the olfactory mucosa (OM). The toxicity of DCBN is mediated by cytochrome P450 (P450)-catalyzed bioactivation; however, it is not known whether target-tissue metabolic activation is essential for toxicity. CYP2A5, expressed abundantly in both liver and OM, was previously found to be one of the P450 enzymes active in DCBN bioactivation in vitro. The aims of this study were to determine the role of CYP2A5 in DCBN toxicity in vivo, by comparing the extents of DCBN toxicity between Cyp2a5-null and wild-type (WT) mice, and to determine whether hepatic microsomal P450 enzymes (including CYP2A5) are essential for the DCBN toxicity, by comparing the extents of DCBN toxicity between liver-Cpr-null (LCN) mice, which have little P450 activity in hepatocytes, and WT mice. We show that the loss of CYP2A5 expression did not alter systemic clearance of DCBN (at 25 mg/kg); but it did inhibit DCBN-induced non-protein thiol depletion and cytotoxicity in the OM. Thus, CYP2A5 plays an essential role in mediating DCBN toxicity in the OM. In contrast to the results seen in the Cyp2a5-null mice, the rates of systemic DCBN clearance were substantially reduced, while the extents of DCBN-induced nasal toxicity were increased, rather than decreased, in the LCN mice, compared to WT mice. Therefore, hepatic P450 enzymes, although essential for DCBN clearance, are not necessary for DCBN-induced OM toxicity. Our findings form the basis for a mechanism-based approach to assessing the potential risks of DCBN nasal toxicity in humans.

  2. Kudzu (Pueraria montana) community responses to herbicides, burning, and high-density loblolly pine

    SciTech Connect (OSTI)

    T.B. Harrington; L.T. Rader-Dixon; J.W. Taylor, Jr.

    2003-11-01

    Kudzu is an aggressive, nonnative vine that currently dominates an estimated 810,000 ha of mesic forest communities in the eastern United States. To test an integrated method of weed control, abundances of kudzu and other plant species were compared during 4 yr after six herbicide treatments (clopyralid, triclopyr, metsulfuron, picloram 1 2,4-D, tebuthiuron, and a nonsprayed check), in which loblolly pines were planted at three densities (0, 1, and 4 seedlings m22) to induce competition and potentially delay kudzu recovery. This split-plot design was replicated on each of the four kudzu-dominated sites near Aiken, SC. Relative light intensity (RLI) and soil water content (SWC) were measured periodically to identify mechanisms of interference among plant species. Two years after treatment (1999), crown coverage of kudzu averaged , 2% in herbicide plots compared with 93% in the nonsprayed check, and these differences were maintained through 2001, except in clopyralid plots where kudzu cover increased to 15%. In 2001, pine interference was associated with 33, 56, and 67% reductions in biomass of kudzu, blackberry, and herbaceous vegetation, respectively. RLI in kudzu-dominated plots (4 to 15% of full sun) generally was less than half that of herbicide-treated plots. SWC was greatest in tebuthiuron plots, where total vegetation cover averaged 26% compared with 77 to 111% in other plots. None of the treatments eradicated kudzu, but combinations of herbicides and induced pine competition delayed its recovery.

  3. Comparing Metal Leaching and Toxicity from High pH, Low pH, and High Ammonia Fly Ash

    SciTech Connect (OSTI)

    Palumbo, Anthony Vito; Phillips, Jana Randolph; Fagan, Lisa Anne; Drake, Meghan M; Ruther, Rose Emily; Fisher, L. Suzanne; Amonette, J. E.

    2007-01-01

    Previous work with both class F and class C fly ash indicated minimal leaching from most fly ashes tested. However, the addition of NOx removal equipment might result in higher levels of ammonia in the fly ash. We have recently been testing fly ash with a wide range of pH (3.7-12.4) originating from systems with NOx removal equipment. Leaching experiments were done using dilute CaCl2 solutions in batch and columns and a batch nitric acid method. All methods indicated that the leaching of heavy metals was different in the highest ammonia sample tested and the high pH sample. However, toxicity testing with the Microtox system has indicated little potential toxicity in leachates except for the fly ash at the highest pH (12.4). When the leachate from the high pH fly ash was neutralized, toxicity was eliminated.

  4. Comparing metal leaching and toxicity from high pH, low pH, and high ammonia fly ash

    SciTech Connect (OSTI)

    Palumbo, Anthony V.; Tarver, Jana R.; Fagan, Lisa A.; McNeilly, Meghan S.; Ruther, Rose; Fisher, L. S.; Amonette, James E.

    2007-07-01

    Previous work with both class F and class C fly ash indicated minimal leaching from most fly ashes tested. However, the addition of NOx removal equipment might result in higher levels of ammonia in the fly ash. We have recently been testing fly ash with a wide range of pH (3.712.4) originating from systems with NOx removal equipment. Leaching experiments were done using dilute CaCl2 solutions in batch and columns and a batch nitric acid method. All methods indicated that the leaching of heavy metals was different in the highest ammonia sample tested and the high pH sample. However, toxicity testing with the Microtox* system has indicated little potential toxicity in leachates except for the fly ash at the highest pH (12.4). When the leachate from the high pH fly ash was neutralized, toxicity was eliminated.

  5. Forestry herbicide influences on biodiversity and wildlife habitats in Southern forests.

    SciTech Connect (OSTI)

    Miller, Karl V.

    2004-01-01

    Abstract In the southern United States, herbicide use continues to increase for timber management in commercial pine (Pinus spp.) plantations, for modifying wildlife habitats, and for invasive plant control. Several studies have reported that single applications of forestry herbicides at stand initiation have minor and temporary impacts on plant communities and wildlife habitat conditions, with some reports of enhanced habitat conditions for both game and nongame species. Due to the high resiliency of floral communities, plant species richness and diversity rebound rapidly after single herbicide treatments, with short- and long-term compositional shifts according to the selectivity and efficacy of the herbicide used. Recently, however, a shift to the Southeast in North American timber supplies has resulted in increased forest management intensity. Current site-preparation techniques rely on herbicide combinations, often coupled with mechanical treatments and >1 years of post-planting applications to enhance the spectrum and duration of vegetation control. This near-total control of associated vegetation at establishment and more rapid pine canopy closure, coupled with shortened and repeated rotations, likely will affect plant diversity and wildlife habitat quality. Development of mitigation methods at the stand and landscape levels will be required to minimize vegetative and wildlife impacts while allowing continued improvement in pine productivity. More uncertain are long-term impacts of increasing invasive plant occupation and the projected increase in herbicide use that will be needed to reverse this worsening situation. In addition, the potential of herbicides to meet wildlife management objectives in areas where traditional techniques have high social costs (e.g., prescribed fire) should be fully explored.

  6. Forestry herbicide influences on biodiversity and wildlife habitat in Southern forests.

    SciTech Connect (OSTI)

    Miller, Karl V.; Miller, James, H.

    2004-07-01

    Abstract In the southern United States, herbicide use continues to increase for timber management in commercial pine (Pinus spp.) plantations, for modifying wildlife habitats, and for invasive plant control. Several studies have reported that single applications of forestry herbicides at stand initiation have minor and temporary impacts on plant communities and wildlife habitat conditions, with some reports of enhanced habitat conditions for both game and nongame species. Due to the high resiliency of floral communities, plant species richness and diversity rebound rapidly after single herbicide treatments, with short- and long-term compositional shifts according to the selectivity and efficacy of the herbicide used. Recently, however, a shift to the Southeast in North American timber supplies has resulted in increased forest management intensity. Current site-preparation techniques rely on herbicide combinations, often coupled with mechanical treatments and >1 years of post-planting applications to enhance the spectrum and duration of vegetation control. This near-total control of associated vegetation at establishment and more rapid pine canopy closure, coupled with shortened and repeated rotations, likely will affect plant diversity and wildlife habitat quality. Development of mitigation methods at the stand and landscape levels will be required to minimize vegetative and wildlife impacts while allowing continued improvement in pine productivity. More uncertain are long-term impacts of increasing invasive plant occupation and the projected increase in herbicide use that will be needed to reverse this worsening situation. In addition, the potential of herbicides to meet wildlife management objectives in areas where traditional techniques have high social costs (e.g., prescribed fire) should be fully explored.

  7. High-Grade Acute Organ Toxicity as a Positive Prognostic Factor in Primary Radiochemotherapy for Anal Carcinoma

    SciTech Connect (OSTI)

    Wolff, Hendrik Andreas; Raus, Ismene; Jung, Klaus; Schueler, Phillip; Herrmann, Markus Karl; Hennies, Steffen; Vorwerk, Hilke; Hille, Andrea; Hess, Clemens Friedrich; Christiansen, Hans

    2011-04-01

    Purpose: To test for a possible correlation between high-grade acute organ toxicity during primary radiochemotherapy and treatment outcome for patients with anal carcinoma. Methods and Materials: From 1991 to 2009, 72 patients with anal carcinoma were treated at our department (10 patients had stage I, 28 patients had stage II, 11 patients had stage IIIA, and 13 patients had stage IIIB cancer [Union Internationale Contre le Cancer criteria]). All patients received normofractionated (1.8 Gy/day, five times/week) whole-pelvis irradiation including iliac and inguinal lymph nodes with a cumulative dose of 50.4 Gy. Concomitant chemotherapy regimen consisted of two cycles of 5-fluorouracil (1,000 mg/m{sup 2}total body surface area (TBSA)/day as continuous intravenous infusion on days 1-4 and 29-32) and mitomycin C (10 mg/m{sup 2}/TBSA, intravenously on days 1 and 29). Toxicity during treatment was monitored weekly, and any incidence of Common Toxicity Criteria (CTC) grade of {>=}3 for skin reaction, cystitis, proctitis, or enteritis was assessed as high-grade acute organ toxicity for later analysis. Results: We found significant correlation between high-grade acute organ toxicity and overall survival, locoregional control, and stoma-free survival, which was independent in multivariate analysis from other possible prognostic factors: patients with a CTC acute organ toxicity grade of {>=}3 had a 5-year overall survival rate of 97% compared to 30% in patients without (p < 0.01, multivariate analysis; 97% vs. 48%, p = 0.03 for locoregional control, and 95% vs. 59%, p = 0.05 for stoma-free survival). Conclusions: Our data indicate that normal tissue and tumor tissue may behave similarly with respect to treatment response, since high-grade acute organ toxicity during radiochemotherapy showed itself to be an independent prognostic marker in our patient population. This hypothesis should be further analyzed by using biomolecular and clinical levels in future clinical trials.

  8. Ultra High Efficiency ESP for Fine Particulate and Air Toxics Control

    SciTech Connect (OSTI)

    Srinivasachar, Srivats; Pease, Benjamin R.; Porle, Kjell; Mauritzson, Christer; Haythornthwaite, Sheila

    1997-07-01

    Nearly ninety percent of U.S. coal-fired utility boilers are equipped with electrostatic precipitators (ESP). Cost effective retrofittable ESP technologies are the only means to accomplish Department of Energy's (DOE) goal of a major reduction in fine particulate and air toxic emissions from coal-fired power plants. Particles in the size range of 0.1 to 5 {micro}m typically escape ESPs. Metals, such as arsenic, cadmium, lead, molybdenum and antimony, concentrate on these particles. This is the main driver for improved fine particulate control. Vapor phase emissions of mercury, selenium and arsenic are also of major concern. Current dry ESPs, which operate at temperatures greater than 280 F, provide little control for vapor phase toxics. The need for inherent improvement to ESPs has to be considered keeping in perspective the current trend towards the use of low sulfur coals. Switching to low sulfur coals is the dominant approach for SO{sub 2} emission reduction in the utility industry. Low sulfur coals generate high resistivity ash, which can cause an undesirable phenomenon called ''back corona.'' Higher particulate emissions occur if there is back corona in the ESP. Results of the pilot-scale testing identified the ''low temperature ESP'' concept to have the biggest impact for the two low sulfur coals investigated. Lowering the flue gas temperature to 220 F provided the maximum impact in terms of decreased emissions. Intermediate operating temperatures (reduction from 340 to 270 F) also gave significant ESP performance improvement. A significant reduction in particulate emissions was also noted when the flue gas humidity was increased (temperature held constant) from the baseline condition for these moderately high resistivity ash coals. Independent control of flue gas humidity and temperature was an important and a notable element in this project. Mercury emissions were also measured as a function of flue gas temperature. Mercury emissions decreased as the flue

  9. EA-2013: Herbicide Application at Three Substations; Imperial...

    Office of Environmental Management (EM)

    Imperial County (California), Maricopa and Yuma Counties (Arizona) EA-2013: Herbicide Application at Three Substations; Imperial County (California), Maricopa and Yuma ...

  10. Rationale for Selection of Pesticides, Herbicides, and Related Compounds from the Hanford SST/DST Waste Considered for Analysis in Support of the Regulatory DQO (Privatization)

    SciTech Connect (OSTI)

    Wiemers, K.D.; Daling, P.; Meier, K.

    1999-01-04

    Regulated pesticides, herbicides, miticides, and fungicides were evaluated for their potential past and current use at the Hanford Site. The starting list of these compounds is based on regulatory analyte input lists discussed in the Regulatory DQO. Twelve pesticide, herbicide, miticide, and fungicide compounds are identified for analysis in the Hanford SST and DST waste in support of the Regulatory DQO. The compounds considered for additional analyses are non-detected, considered stable in the tank waste matrix, and of higher toxicity/carcinogenicity.

  11. Gene encoding herbicide safener binding protein

    DOE Patents [OSTI]

    Walton, Jonathan D.; Scott-Craig, John S.

    1999-01-01

    The cDNA encoding safener binding protein (SafBP), also referred to as SBP1, is set forth in FIG. 5 and SEQ ID No. 1. The deduced amino acid sequence is provided in FIG. 5 and SEQ ID No. 2. Methods of making and using SBP1 and SafBP to alter a plant's sensitivity to certain herbicides or a plant's responsiveness to certain safeners are also provided, as well as expression vectors, transgenic plants or other organisms transfected with said vectors and seeds from said plants.

  12. Inorganic–organic hybrids presenting high basic center content: SBA-15 incorporation, toxic metals sorption and energetic behavior

    SciTech Connect (OSTI)

    Oliveira, Fernando J.V.E.; Melo, Maurício A.; Airoldi, Claudio

    2013-03-15

    Highlights: ► Mesoporous SBA-15 silicas were organofunctionalized with new silylant agents. ► Thiocarbamate was used to enhance the silylating agent chains and basic centers. ► The synthesized pendant chains contain nitrogen and sulfur basic centers. ► The new hybrids sorb toxic cations from aqueous solutions with high efficiency. ► The thermodynamic data demonstrated favorable cation/basic center interactions. - Abstract: Mesoporous SBA-15 samples were organofunctionalized with mono, di- and tri-aminosilanes that previously reacted with thiocarbamide to enhance the organic chains and attach nitrogen and sulfur basic centers to the surface of the solids. These new organosilanes were synthesized through a non-solvent approach to reduce both cost and hazardous wastes. The high affinities for both hard and soft Lewis acids due to the combination of nitrogen and sulfur atoms attached to the same pendant chain enabled favorable sorption capacities for Cu{sup 2+}, Cd{sup 2+} and Pb{sup 2+} cations, with maximum capacities of 1.90, 3.48 and 5.30 mmol g{sup −1}, respectively, for the most efficient mesoporous silica. Microcalorimetric investigations allowed the calculation of the thermodynamic data at the solid/liquid interface. All Gibbs energy are negative as expected for spontaneous cation/basic center interactions and the positive entropic values from 49 ± 3 to 108 ± 5 J K{sup −1} mol{sup −1}, also reinforced this favorable interactive process in heterogeneous system. The designed organosilanes covalently bonded to the inorganic siliceous skeleton can be suggested as new materials for toxic metal removal from a wastewater with high efficiency.

  13. Gender-specific reduction of hepatic Mrp2 expression by high-fat diet protects female mice from ANIT toxicity

    SciTech Connect (OSTI)

    Kong, Bo; Csanaky, Ivn L.; Aleksunes, Lauren M.; Patni, Meghan; Chen, Qi; Ma, Xiaochao; Jaeschke, Hartmut; Weir, Scott; Broward, Melinda; Klaassen, Curtis D.; University of Kansas Cancer Center, Kansas City, KS ; Guo, Grace L.

    2012-06-01

    Emerging evidence suggests that feeding a high-fat diet (HFD) to rodents affects the expression of genes involved in drug transport. However, gender-specific effects of HFD on drug transport are not known. The multidrug resistance-associated protein 2 (Mrp2, Abcc2) is a transporter highly expressed in the hepatocyte canalicular membrane and is important for biliary excretion of glutathione-conjugated chemicals. The current study showed that hepatic Mrp2 expression was reduced by HFD feeding only in female, but not male, C57BL/6J mice. In order to determine whether down-regulation of Mrp2 in female mice altered chemical disposition and toxicity, the biliary excretion and hepatotoxicity of the Mrp2 substrate, ?-naphthylisothiocyanate (ANIT), were assessed in male and female mice fed control diet or HFD for 4 weeks. ANIT-induced biliary injury is a commonly used model of experimental cholestasis and has been shown to be dependent upon Mrp2-mediated efflux of an ANIT glutathione conjugate that selectively injures biliary epithelial cells. Interestingly, HFD feeding significantly reduced early-phase biliary ANIT excretion in female mice and largely protected against ANIT-induced liver injury. In summary, the current study showed that, at least in mice, HFD feeding can differentially regulate Mrp2 expression and function and depending upon the chemical exposure may enhance or reduce susceptibility to toxicity. Taken together, these data provide a novel interaction between diet and gender in regulating hepatobiliary excretion and susceptibility to injury. -- Highlights: ? High-fat diet decreases hepatic Mrp2 expression only in female but not in male mice. ? HFD significantly reduces early-phase biliary ANIT excretion in female mice. ? HFD protects female mice against ANIT-induced liver injury.

  14. Long-Term Efficacy and Toxicity of Low-Dose-Rate {sup 125}I Prostate Brachytherapy as Monotherapy in Low-, Intermediate-, and High-Risk Prostate Cancer

    SciTech Connect (OSTI)

    Kittel, Jeffrey A.; Reddy, Chandana A.; Smith, Kristin L.; Stephans, Kevin L.; Tendulkar, Rahul D.; Ulchaker, James; Angermeier, Kenneth; Campbell, Steven; Stephenson, Andrew; Klein, Eric A.; Wilkinson, D. Allan; Ciezki, Jay P.

    2015-07-15

    Purpose/Objectives: To report long-term efficacy and toxicity for a single-institution cohort of patients treated with low-dose-rate prostate brachytherapy permanent implant (PI) monotherapy. Methods and Materials: From 1996 to 2007, 1989 patients with low-risk (61.3%), intermediate-risk (29.8%), high-intermediate-risk (4.5%), and high-risk prostate cancer (4.4%) were treated with PI and followed up prospectively in a registry. All patients were treated with {sup 125}I monotherapy to 144 Gy. Late toxicity was coded retrospectively according to a modified Common Terminology Criteria for Adverse Events 4.0 scale. The rates of biochemical relapse-free survival (bRFS), distant metastasis-free survival (DMFS), overall survival (OS), and prostate cancer–specific mortality (PCSM) were calculated. We identified factors associated with late grade ≥3 genitourinary (GU) and gastrointestinal (GI) toxicity, bRFS, DMFS, OS, PCSM, and incontinence. Results: The median age of the patients was 67 years, and the median overall and prostate-specific antigen follow-up times were 6.8 years and 5.8 years, respectively. The overall 5-year rates for bRFS, DMFS, OS, and PCSM were 91.9%, 97.8%, 93.7%, and 0.71%, respectively. The 10-year rates were 81.5%, 91.5%, 76.1%, and 2.5%, respectively. The overall rates of late grade ≥3 GU and GI toxicity were 7.6% and 0.8%, respectively. On multivariable analysis, age and prostate length were significantly associated with increased risk of late grade ≥3 GU toxicity. The risk of incontinence was highly correlated with both pre-PI and post-PI transurethral resection of the prostate. Conclusions: Prostate brachytherapy as monotherapy is an effective treatment for low-risk and low-intermediate-risk prostate cancer and appears promising as a treatment for high-intermediate-risk and high-risk prostate cancer. Significant long-term toxicities are rare when brachytherapy is performed as monotherapy.

  15. Toxic remediation

    DOE Patents [OSTI]

    Matthews, Stephen M.; Schonberg, Russell G.; Fadness, David R.

    1994-01-01

    What is disclosed is a novel toxic waste remediation system designed to provide on-site destruction of a wide variety of hazardous organic volatile hydrocarbons, including but not limited to halogenated and aromatic hydrocarbons in the vapor phase. This invention utilizes a detoxification plenum and radiation treatment which transforms hazardous organic compounds into non-hazardous substances.

  16. Leaching and persistence of herbicides for kudzu (Pueraria montana) control on pine regeneration sites

    SciTech Connect (OSTI)

    Berisford, Yvette, C.; Bush, Parshall, B.; Taylor, John, W.

    2006-03-01

    Kudzu is an exotic vine that threatens forests in the southeastern United States. It can climb, overtop, and subsequently kill new seedlings or mature trees. Herbicides are commonly used to control kudzu; however, eradication might require retreatment for 3 to 10 yr in young stands and 7 to 10 yr for mature stands. Clopyralid, picloram, triclopyr, metsulfuron, and tebuthiuron exert various degrees of control, depending on soil type, meteorological conditions, herbicide formulation, seasonal application, characteristics of the kudzu stand, and frequency and number of herbicide. Field residue data for soil or leachate are lacking for all of these herbicides when they are used in actual forest regeneration programs in the Coastal Plain. These data are needed to assess the relative potential for the herbicides to leach into groundwater or to move off-site into sensitive ecological areas of the Coastal Plain in which sandy soils predominate and the groundwater tends to be shallow. As part of an integrated pest management program to control kudzu on forest regeneration areas at the Savannah River Site near New Ellenton, SC, five herbicides were evaluated from the standpoints of herbicide leaching, kudzu control, and plant community development. Three herbicide chemical families were represented. This included pyridinecarboxylic acid herbicides (clopyralid, picloram 1 2,4-D, and triclopyr), a sulfonylurea herbicide (metsulfuron), and a substituted urea herbicide (tebuthiuron).

  17. Long-term Survival and Toxicity in Patients Treated With High-Dose Intensity Modulated Radiation Therapy for Localized Prostate Cancer

    SciTech Connect (OSTI)

    Spratt, Daniel E.; Pei, Xin; Yamada, Josh; Kollmeier, Marisa A.; Cox, Brett; Zelefsky, Michael J.

    2013-03-01

    Purpose: To report long-term survival and toxicity outcomes with the use of high-dose intensity modulated radiation therapy (IMRT) to 86.4 Gy for patients with localized prostate cancer. Methods and Materials: Between August 1997 and December 2008, 1002 patients were treated to a dose of 86.4 Gy using a 5-7 field IMRT technique. Patients were stratified by prognostic risk group based on National Comprehensive Cancer Network risk classification criteria. A total of 587 patients (59%) were treated with neoadjuvant and concurrent androgen deprivation therapy. The median follow-up for the entire cohort was 5.5 years (range, 1-14 years). Results: For low-, intermediate-, and high-risk groups, 7-year biochemical relapse-free survival outcomes were 98.8%, 85.6%, and 67.9%, respectively (P<.001), and distant metastasis-free survival rates were 99.4%, 94.1%, and 82.0% (P<.001), respectively. On multivariate analysis, T stage (P<.001), Gleason score (P<.001), and >50% of initial biopsy positive core (P=.001) were predictive for distant mestastases. No prostate cancer-related deaths were observed in the low-risk group. The 7-year prostate cancer-specific mortality (PCSM) rates, using competing risk analysis for intermediate- and high-risk groups, were 3.3% and 8.1%, respectively (P=.008). On multivariate analysis, Gleason score (P=.004), percentage of biopsy core positivity (P=.003), and T-stage (P=.033) were predictive for PCSM. Actuarial 7-year grade 2 or higher late gastrointestinal and genitourinary toxicities were 4.4% and 21.1%, respectively. Late grade 3 gastrointestinal and genitourinary toxicity was experienced by 7 patients (0.7%) and 22 patients (2.2%), respectively. Of the 427 men with full potency at baseline, 317 men (74%) retained sexual function at time of last follow-up. Conclusions: This study represents the largest cohort of patients treated with high-dose radiation to 86.4 Gy, using IMRT for localized prostate cancer, with the longest follow-up to date

  18. Microsoft Word - BLM WAPA Herbicide Use FINAL working20160119.docx

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    the Interior Bureau of Land Management And U.S. Department of Energy Western Area Power Administration _________________________________ Environmental Assessment DOI-BLM-AZ-P020-2016-0005-EA DOE/EA-2013 January 25, 2016 HERBICIDE APPLICATION AT THREE WESTERN AREA POWER ADMINISTRATION SUBSTATIONS Lower Sonoran Field Office 21605 North 7 th Avenue Phoenix, Arizona 85027 Western Area Power Administration Desert Southwest Region P.O. Box 6457 Phoenix, Arizona 85005 DOI-BLM-AZ-P020-2016-0005-EA

  19. Metallothionein protection of cadmium toxicity

    SciTech Connect (OSTI)

    Klaassen, Curtis D. Liu, Jie; Diwan, Bhalchandra A.

    2009-08-01

    The discovery of the cadmium (Cd)-binding protein from horse kidney in 1957 marked the birth of research on this low-molecular weight, cysteine-rich protein called metallothionein (MT) in Cd toxicology. MT plays minimal roles in the gastrointestinal absorption of Cd, but MT plays important roles in Cd retention in tissues and dramatically decreases biliary excretion of Cd. Cd-bound to MT is responsible for Cd accumulation in tissues and the long biological half-life of Cd in the body. Induction of MT protects against acute Cd-induced lethality, as well as acute toxicity to the liver and lung. Intracellular MT also plays important roles in ameliorating Cd toxicity following prolonged exposures, particularly chronic Cd-induced nephrotoxicity, osteotoxicity, and toxicity to the lung, liver, and immune system. There is an association between human and rodent Cd exposure and prostate cancers, especially in the portions where MT is poorly expressed. MT expression in Cd-induced tumors varies depending on the type and the stage of tumor development. For instance, high levels of MT are detected in Cd-induced sarcomas at the injection site, whereas the sarcoma metastases are devoid of MT. The use of MT-transgenic and MT-null mice has greatly helped define the role of MT in Cd toxicology, with the MT-null mice being hypersensitive and MT-transgenic mice resistant to Cd toxicity. Thus, MT is critical for protecting human health from Cd toxicity. There are large individual variations in MT expression, which might in turn predispose some people to Cd toxicity.

  20. Nanoparticle toxicity testing

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    submit Nanoparticle toxicity testing Assessing the potential health hazards of nanotechnology March 25, 2013 Robot In the search for more accurate and efficient techniques to...

  1. Ross Hazardous and Toxic Materials Handling Facility: Environmental Assessment.

    SciTech Connect (OSTI)

    URS Consultants, Inc.

    1992-06-01

    The Bonneville Power Administration (BPA) owns a 200-acre facility in Washington State known as the Ross Complex. Activities at the Ross Complex routinely involve handling toxic substances such as oil-filled electrical equipment containing polychlorinated biphenyls (PCBs), organic and inorganic compounds for preserving wood transmission poles, and paints, solvents, waste oils, and pesticides and herbicides. Hazardous waste management is a common activity on-site, and hazardous and toxic substances are often generated from these and off-site activities. The subject of this environmental assessment (EA) concerns the consolidation of hazardous and toxic substances handling at the Complex. This environmental assessment has been developed to identify the potential environmental impacts of the construction and operation of the proposal. It has been prepared to meet the requirements of the National Environmental Policy Act (NEPA) to determine if the proposed action is likely to have a significant impact on the environment. In addition to the design elements included within the project, mitigation measures have been identified within various sections that are now incorporated within the project. This facility would be designed to improve the current waste handling practices and to assist BPA in meeting Federal and state regulations.

  2. Modified cellulose synthase gene from Arabidopsis thaliana confers herbicide resistance to plants

    DOE Patents [OSTI]

    Somerville, Chris R.; Scheible, Wolf

    2007-07-10

    Cellulose synthase ("CS"), a key enzyme in the biosynthesis of cellulose in plants is inhibited by herbicides comprising thiazolidinones such as 5-tert-butyl-carbamoyloxy-3-(3-trifluromethyl)phenyl-4-thiazolidinone (TZ), isoxaben and 2,6-dichlorobenzonitrile (DCB). Two mutant genes encoding isoxaben and TZ-resistant cellulose synthase have been isolated from isoxaben and TZ-resistant Arabidopsis thaliana mutants. When compared with the gene coding for isoxaben or TZ-sensitive cellulose synthase, one of the resistant CS genes contains a point mutation, wherein glycine residue 998 is replaced by an aspartic acid. The other resistant mutation is due to a threonine to isoleucine change at amino acid residue 942. The mutant CS gene can be used to impart herbicide resistance to a plant; thereby permitting the utilization of the herbicide as a single application at a concentration which ensures the complete or substantially complete killing of weeds, while leaving the transgenic crop plant essentially undamaged.

  3. EA-2013: Herbicide Application at Three Substations; Imperial County (California), Maricopa and Yuma Counties (Arizona)

    Office of Energy Efficiency and Renewable Energy (EERE)

    Western Area Power Administration (Western) and the Bureau of Land Management (BLM) prepared an EA that analyzes the potential environmental impacts of Western’s proposed use of selected herbicides for the treatment of undesirable vegetation within three existing substations on lands administered by BLM.

  4. Inhibition of acetyl-coenzyme A carboxylase by two classes of grass-selective herbicides

    SciTech Connect (OSTI)

    Rendina, A.R.; Craig-Kennard, A.C.; Beaudoin, J.D.; Breen, M.K. )

    1990-05-01

    The selective grass herbicides diclofop, haloxyfop, and trifop (((aryloxy)phenoxy)propionic acids) and alloxydim, sethoxydim, and clethodim (cyclohexanediones) are potent, reversible inhibitors of acetyl-coenzyme A carboxylase (ACC) partially purified from barley, corn, and wheat. Although inhibition of the wheat enzyme by clethodim and diclofop is noncompetitive versus each of the substrates adenosine triphosphate (ATP), HCO{sub 3}{sup {minus}}, and acetyl-coenzyme A (acetyl-CoA), diclofop and clethodim are nearly competitive versus acetyl-CoA since the level of inhibition is most sensitive to the concentration of acetyl-CoA (K{sub is} < K{sub ii}). To conclusively show whether the herbicides interact at the biotin carboxylation site or the carboxyl transfer site, the inhibition of isotope exchange and partial reactions catalyzed at each site was studied with the wheat enzyme. Only the ({sup 14}C)acetyl-CoA-malonyl-CoA exchange and decarboxylation of ({sup 14}C)malonyl-CoA reactions are strongly inhibited by clethodim and diclofop, suggesting that the herbicides interfere with the carboxyl transfer site rather than the biotin carboxylation site of the enzyme. Double-inhibition studies with diclofop and clethodim suggest that the ((aryloxy)phenoxy)propionic acid and cyclohexanedione herbicides may bind to the same region of the enzyme.

  5. Investigating Sources of Toxicity in Stormwater: Algae Mortality in Runoff Upstream of the Lawrence Livermore National Laboratory

    SciTech Connect (OSTI)

    Campbell, C G; Folks, K; Mathews, S; Martinelli, R

    2003-10-06

    A source evaluation case study is presented for observations of algae toxicity in an intermittent stream passing through the Lawrence Livermore National Laboratory near Livermore, California. A five-step procedure is discussed to determine the cause of water toxicity problems and to determine appropriate environmental management practices. Using this approach, an upstream electrical transfer station was identified as the probable source of herbicides causing the toxicity. In addition, an analytical solution for solute transport in overland flow was used to estimate the application level of 40 Kg/ha. Finally, this source investigation demonstrates that pesticides can impact stream water quality regardless of application within levels suggested on manufacturer labels. Environmental managers need to ensure that pesticides that could harm aquatic organisms (including algae) not be used within close proximity to streams or storm drainages and that application timing should be considered for environmental protection.

  6. Toxicity of stormwater treatment pond sediments to Hyalella azteca (Amphipoda)

    SciTech Connect (OSTI)

    Karouna-Renier, N.K.; Sparling, D.W.

    1997-04-01

    Stormwater runoff from highways and commercial, industrial, and residential areas contains a wide spectrum of pollutants including heavy metals, petroleum hydrocarbons, pesticides, herbicides, sediment, and nutrients. Recent efforts to reduce the impacts of urbanization on natural wetlands and other receiving waters have included the construction of stormwater treatment ponds and wetlands. These systems provide flood control and improve water quality through settling, adsorption, and precipitation of pollutants removing up to 95% of metals, nutrients and sediment before discharged from the site. The design of stormwater ponds to provide habitat for aquatic wildlife has prompted concern over the potential exposure of aquatic organisms to these contaminants. Aquatic sediments concentrate a wide array of organic and inorganic pollutants. Although water quality criteria may not be exceeded, organisms living in or near the sediments may be adversely affected. The availability of chemicals in sediments depends strongly on the prevailing chemistry. Physical conditions of the sediment and water quality characteristics including pH, redox potential and hardness, also influence contaminant availability. Studies have shown that heavy metals and nutrients carried by runoff concentrate in the sediment of stormwater ponds. Although several investigations have assessed the toxicity of sediments in streams receiving urban runoff, there have been few studies of the toxicity of stormwater treatment pond sediments to aquatic organisms. This study was part of a large-scale assessment of the contaminant hazards of stormwater treatment ponds. The objective of this study was to evaluate the toxicity of sediments and water from stormwater ponds over a 10-d period to juvenile Hyalella azteca. Bioassay results were related to concentrations of acid volatile sulfides and metals of the tested sediments. 17 refs., 4 tabs.

  7. Toxic Substances Control Act

    SciTech Connect (OSTI)

    Not Available

    1992-05-15

    This Reference Book contains a current copy of the Toxic Substances Control Act and those regulations that implement the statute and appear to be most relevant to DOE activities. The document is provided to DOE and contractor staff for informational purposes only and should not be interpreted as legal guidance. Questions concerning this Reference Book may be directed to Mark Petts, EH-231 (202/586-2609).

  8. How toxic is coal ash? A laboratory toxicity case study

    SciTech Connect (OSTI)

    Sherrard, Rick M.; Carriker, Neil; Greeley, Jr., Mark Stephen

    2014-12-08

    Under a consent agreement among the Environmental Protection Agency (EPA) and proponents both for and against stricter regulation, EPA is to issue a new coal ash disposal rule by the end of 2014. Laboratory toxicity investigations often yield conservative estimates of toxicity because many standard test species are more sensitive than resident species, thus could provide information useful to the rule-making. However, few laboratory studies of coal ash toxicity are available; most studies reported in the literature are based solely on field investigations. In this paper, we describe a broad range of toxicity studies conducted for the Tennessee Valley Authority (TVA) Kingston ash spill, results of which help provide additional perspective on the toxicity of coal ash.

  9. How toxic is coal ash? A laboratory toxicity case study

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Sherrard, Rick M.; Carriker, Neil; Greeley, Jr., Mark Stephen

    2014-12-08

    Under a consent agreement among the Environmental Protection Agency (EPA) and proponents both for and against stricter regulation, EPA is to issue a new coal ash disposal rule by the end of 2014. Laboratory toxicity investigations often yield conservative estimates of toxicity because many standard test species are more sensitive than resident species, thus could provide information useful to the rule-making. However, few laboratory studies of coal ash toxicity are available; most studies reported in the literature are based solely on field investigations. In this paper, we describe a broad range of toxicity studies conducted for the Tennessee Valley Authoritymore » (TVA) Kingston ash spill, results of which help provide additional perspective on the toxicity of coal ash.« less

  10. Studies on the mechanisms of action of the herbicide safener CGA-92194

    SciTech Connect (OSTI)

    Zama, P.

    1986-01-01

    CGA-92194 is a herbicide safener that is used as a seed dressing agent to protect grain sorghum against metolachlor injury. The potential adverse phytotoxic effects and the mechanisms of the protective action of this safener were studied in laboratory experiments. Adverse phytotoxicity was assessed by comparing CGA-92194 and the herbicide safeners cyometrinil and flurazole for their effects on CO/sub 2/ fixation, protein, DNA, RNA and lipid synthesis of enzymatically isolated leaf cells of soybean. The safening action mechanisms of CGA-92194 were studied by examining the potential interactions of this safener with metolachlor at the levels of uptake and macromolecular syntheses in enzymatically isolated leaf mesophyll protoplasts of grain sorghum. When CGA-92194 and metolachlor were given simultaneously, CGA-92194 enhanced /sup 14/C-metolachlor uptake into the sorghum protoplasts in a concentration-dependent pattern. Treatments with metolachlor and CGA-92194 in combination inhibited the incorporation of /sup 14/C-uracil, /sup 3/H-thymidine and /sup 14/C-acetate into sorghum protoplast macromolecules less than metolachlor given alone, suggesting the potential involvement of a competitive antagonism in CGA-92194 mechanism of action. The metabolic activity and growth of sorghum seedlings grown from CGA-92194-pretreated seeds were lower than that of seedlings grown from untreated seeds at 10 or 20 days after planting. These results indicate that a safener-induced stimulation of the spontaneous or enzymatic conjugation of metolachlor with GSH is most likely involved in CGA-92194 protective action.

  11. VARIATIONS IN REPRODUCTIVE TOXICANT IDENTIFICATION

    SciTech Connect (OSTI)

    Simmons, F

    2008-05-13

    Reproductive toxicants are a very important class of compounds. They present unique hazards to those of child bearing ages, perform their 'dirty work' using a wide variety of mechanisms on a number of different organs, and are regulatorily important. Because of all of this, properly identifying reproductive toxicants is important, but fraught with difficulty. In this paper we will describe types or reproductive toxicants, their importance, and both mistakes and good practices that people who are not experts in reproductive toxicology may use in their attempts to identify them. Additionally, this paper will focus on chemical reproductive toxicants and will not address biological agents that could affect reproductive toxicity although many principles outlined here could be applied to that endeavor.

  12. Priorities for toxic wastewater management in Pakistan

    SciTech Connect (OSTI)

    Rahman, A.

    1996-12-31

    This study assesses the number of industries in Pakistan, the total discharge of wastewater, the biological oxygen demand (BOD) load, and the toxicity of the wastewater. The industrial sector is a major contributor to water pollution, with high levels of BOD, heavy metals, and toxic compounds. Only 30 industries have installed water pollution control equipment, and most are working at a very low operational level. Priority industrial sectors for pollution control are medium- to large-scale textile industries and small-scale tanneries and electroplating industries. Each day the textile industries discharge about 85,000 m{sup 3} of wastewater with a high BOD, while the electroplating industries discharge about 23,000 m{sup 3} of highly toxic and hazardous wastewater. Various in-plant modifications can reduce wastewater discharges. Economic incentives, like tax rebates, subsidies, and soft loans, could be an option for motivating medium- to large-scale industries to control water pollution. Central treatment plants may be constructed for treating wastewater generated by small-scale industries. The estimated costs for the treatment of textile and electroplating wastewater are given. The legislative structure in Pakistan is insufficient for control of industrial pollution; not only do existing laws need revision, but more laws and regulations are needed to improve the state of affairs, and enforcement agencies need to be strengthened. 15 refs., 1 fig., 9 tabs.

  13. Toxicity of Uranium Adsorbent Materials using the Microtox Toxicity Test

    SciTech Connect (OSTI)

    Park, Jiyeon; Jeters, Robert T.; Gill, Gary A.; Kuo, Li-Jung; Bonheyo, George T.

    2015-10-01

    The Marine Sciences Laboratory at the Pacific Northwest National Laboratory evaluated the toxicity of a diverse range of natural and synthetic materials used to extract uranium from seawater. The uranium adsorbent materials are being developed as part of the U. S. Department of Energy, Office of Nuclear Energy, Fuel Resources Program. The goal of this effort was to identify whether deployment of a farm of these materials into the marine environment would have any toxic effects on marine organisms.

  14. California Environmental Protection Agency Department of Toxic...

    Open Energy Info (EERE)

    Department of Toxic Substances Control Jump to: navigation, search Name: California Environmental Protection Agency Department of Toxic Substances Control Place: Sacramento,...

  15. Disposition of toxic PCB congeners in snapping turtle eggs: expressed as toxic equivalents of TCDD

    SciTech Connect (OSTI)

    Bryan, A.M.; Stone, W.B.; Olafsson, P.G.

    1987-11-01

    Studies of snapping turtles, taken from the region of the Upper Hudson River, in New York State, revealed exceedingly high levels of PCBs in the adipose tissue. There is evidence to suggest that large reserves of fat provide protection against chlorinated hydrocarbon toxicity. Such storage may protect snapping turtle eggs from disposition of toxic PCB congeners and account for the apparent absence of reports regarding detrimental effects on the hatchability of eggs from turtles living in the vicinity of the upper Hudson River. The present study was undertaken to determine if indeed these eggs are protected against disposition of toxic PCB congeners by the presence of large reserves of fat. Although tissue volumes play an important role in determining the initial site of disposition, the major factor controlling the elimination of these compounds involves metabolism. For simple halogenated benzenes as well as for more complex halogenated biphenyls, oxidative metabolism catalyzed by P-448, occurs primarily at the site of two adjacent unsubstituted carbon atoms via arene oxide formation leading to the formation of water soluble metabolites. Toxicological studies have demonstrated that the most toxic PCB congeners, isosteriomers of tetrachlorodibenzo-p-dioxin (TCDD), require no metabolic activation. These compounds have chlorine atoms in the meta and para positions of both rings. It may be concluded that the structures of PCB congeners and isomers which favor induction of cytochrome P-448 are also those which are toxic and resist metabolism. It is the objective of the present study to determine if the heavy fat bodies of the female turtle provide a sufficiently large sink to retain the toxic congeners and prevent their incorporation into the eggs.

  16. Use of toxicity testing to evaluate performance of a stormwater treatment marsh

    SciTech Connect (OSTI)

    Katznelson, R.; Jewell, W.T.; Anderson, S.L.

    1994-12-31

    The use of toxicity assessments as a component of constructed wetlands design was addressed in Crandall Creek and downstream Demonstration urban Stormwater Treatment (DUST) marsh in Fremont, CA. Median time to lethality (LT{sub 50}) was used to compare relative intensities of toxicity while electrical conductivity measurements were used to trace the flow of low conductivity stormwater. Measurements taken during or shortly after storm events showed horizontal and vertical gradients in LT{sub 50} and conductivity with high correlation. Toxic stormwater was contained within the marsh after small and medium sized (0.2--1.0 inch) storms. The intensity of toxicity was greatly reduced upon mixing of stormwater with preexisting marsh water. A toxicity dilution model, based on an empirically established relationship between LT{sub 50} and sample dilution, was used to predict toxicity reduction based on dilution alone. Comparison of predicted LT{sub 50} with observed values showed substantial toxicity reduction cannot be explained by dilution only, indicating other removal processes such as sequestration or degradation. Mixing of the water column increased the rate of toxicity diminution in comparison to the rate observed in the unmixed marsh water. Filtration of DUST marsh samples revealed toxicity was associated with the soluble fraction of samples. Phase 1 TIE and metals analyses indicated toxicity was caused by oxidizable, non-polar organics rather than metals. Results of this study indicate the potential use of toxicity assessments as an integral component of wetlands design and management.

  17. Toxic Remediation System And Method

    DOE Patents [OSTI]

    Matthews, Stephen M.; Schonberg, Russell G.; Fadness, David R.

    1996-07-23

    What is disclosed is a novel toxic waste remediation system designed to provide on-site destruction of a wide variety of hazardous organic volatile hydrocarbons, including but not limited to halogenated and aromatic hydrocarbons in the vapor phase. This invention utilizes a detoxification plenum and radiation treatment which transforms hazardous organic compounds into non-hazardous substances.

  18. Toxicity evaluation and hazard review Cold Smoke

    SciTech Connect (OSTI)

    Archuleta, M.M.; Stocum, W.E.

    1993-12-01

    Cold Smoke is a dense white smoke produced by the reaction of titanium tetrachloride and aqueous ammonia aerosols. Early studies on the toxicity of this nonpyrotechnically generated smoke indicated that the smoke itself is essentially non-toxic (i.e. exhibits to systemic toxicity or organ damage due to exposure) under normal deployment conditions. The purpose of this evaluation was to review and summarize the recent literature data available on the toxicity of Cold Smoke, its chemical constituents, and its starting materials.

  19. Pharmacokinetic drivers of toxicity for basic molecules: Strategy to lower pKa results in decreased tissue exposure and toxicity for a small molecule Met inhibitor

    SciTech Connect (OSTI)

    Diaz, Dolores; Ford, Kevin A.; Hartley, Dylan P.; Harstad, Eric B.; Cain, Gary R.; Achilles-Poon, Kirsten; Nguyen, Trung; Peng, Jing; Zheng, Zhong; Merchant, Mark; Sutherlin, Daniel P.; Gaudino, John J.; Kaus, Robert; Lewin-Koh, Sock C.; Choo, Edna F.; Liederer, Bianca M.; Dambach, Donna M.

    2013-01-01

    Several toxicities are clearly driven by free drug concentrations in plasma, such as toxicities related to on-target exaggerated pharmacology or off-target pharmacological activity associated with receptors, enzymes or ion channels. However, there are examples in which organ toxicities appear to correlate better with total drug concentrations in the target tissues, rather than with free drug concentrations in plasma. Here we present a case study in which a small molecule Met inhibitor, GEN-203, with significant liver and bone marrow toxicity in preclinical species was modified with the intention of increasing the safety margin. GEN-203 is a lipophilic weak base as demonstrated by its physicochemical and structural properties: high LogD (distribution coefficient) (4.3) and high measured pKa (7.45) due to the basic amine (N-ethyl-3-fluoro-4-aminopiperidine). The physicochemical properties of GEN-203 were hypothesized to drive the high distribution of this compound to tissues as evidenced by a moderately-high volume of distribution (Vd > 3 l/kg) in mouse and subsequent toxicities of the compound. Specifically, the basicity of GEN-203 was decreased through addition of a second fluorine in the 3-position of the aminopiperidine to yield GEN-890 (N-ethyl-3,3-difluoro-4-aminopiperidine), which decreased the volume of distribution of the compound in mouse (Vd = 1.0 l/kg), decreased its tissue drug concentrations and led to decreased toxicity in mice. This strategy suggests that when toxicity is driven by tissue drug concentrations, optimization of the physicochemical parameters that drive tissue distribution can result in decreased drug concentrations in tissues, resulting in lower toxicity and improved safety margins. -- Highlights: ? Lower pKa for a small molecule: reduced tissue drug levels and toxicity. ? New analysis tools to assess electrostatic effects and ionization are presented. ? Chemical and PK drivers of toxicity can be leveraged to improve safety.

  20. Mutation assays involving blood cells that metabolize toxic substances

    DOE Patents [OSTI]

    Crespi, Charles L.; Thilly, William G.

    1985-01-01

    A line of human blood cells which have high levels of oxidative activity (such as oxygenase, oxidase, peroxidase, and hydroxylase activity) is disclosed. Such cells grow in suspension culture, and are useful to determine the mutagenicity of xenobiotic substances that are metabolized into toxic or mutagenic substances. Mutation assays using these cells, and other cells with similar characteristics, are also disclosed.

  1. Mutation assays involving blood cells that metabolize toxic substances

    DOE Patents [OSTI]

    Crespi, C.L.; Thilly, W.G.

    1999-08-10

    The present invention pertains to a line of human blood cells which have high levels of oxidative activity (such as oxygenase, oxidase, peroxidase, and hydroxylase activity). Such cells grow in suspension culture, and are useful to determine the mutagenicity of xenobiotic substances that are metabolized into toxic or mutagenic substances. The invention also includes mutation assays using these cells, and other cells with similar characteristics. 3 figs.

  2. Mutation assays involving blood cells that metabolize toxic substances

    DOE Patents [OSTI]

    Crespi, Charles L.; Thilly, William G.

    1999-01-01

    The present invention pertains to a line of human blood cells which have high levels of oxidative activity (such as oxygenase, oxidase, peroxidase, and hydroxylase activity). Such cells grow in suspension culture, and are useful to determine the mutagenicity of xenobiotic substances that are metabolized into toxic or mutagenic substances. The invention also includes mutation assays using these cells, and other cells with similar characteristics.

  3. Enhanced toxic cloud knockdown spray system for decontamination applications

    DOE Patents [OSTI]

    Betty, Rita G.; Tucker, Mark D.; Brockmann, John E.; Lucero, Daniel A.; Levin, Bruce L.; Leonard, Jonathan

    2011-09-06

    Methods and systems for knockdown and neutralization of toxic clouds of aerosolized chemical or biological warfare (CBW) agents and toxic industrial chemicals using a non-toxic, non-corrosive aqueous decontamination formulation.

  4. Renewable, Non-Toxic and Cost Competitive Solvents and Plasticizers...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Renewable, Non-Toxic and Cost Competitive Solvents and Plasticizers Renewable, Non-Toxic and Cost Competitive Solvents and Plasticizers Breakout Session 1-D: The Pitch Renewable, ...

  5. Relationship Between Composition and Toxicity of Engine Emission...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Lung Toxicity and Mutagenicity of Emissions From Heavy-Duty Compressed Natural Gas (CNG)-Powered Vehicles Comparative Toxicity of Combined Particle and Semi-Volatile Organic ...

  6. Comparative Toxicity of Combined Particle and Semi-Volatile Organic...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Toxicity of Combined Particle and Semi-Volatile Organic Fractioins of Gasoline and Diesel Emissions Comparative Toxicity of Combined Particle and Semi-Volatile Organic Fractioins of ...

  7. Evaluations in support of regulatory and research decisions by the U. S. Environmental Protection Agency for the control of toxic hazards from hazardous wastes, glyphosate, dalapon, and synthetic fuels

    SciTech Connect (OSTI)

    Scofield, R.

    1984-01-01

    This report includes toxicological and regulatory evaluations performed in support of U.S. EPA regulation of toxic materials and hazardous wastes. The first section of the report describes evaluations which support: (a) the regulation of small-volume generators of hazardous wastes, (b) the regulation of hazardous wastes from pesticide manufacturing, and (c) the disposal of the herbicide, silvex. The second section describes the environmental fate, transport, and effect of glyphosate and dalapon. The third section deals with synthetic fuels, including evaluations of synfuel-product toxicity, uncontrolled air emissions, and particular focus on the toxicity of products from several indirect coal liquefaction processes including methanol synthesis, Fischer-Tropsch, Mobil M-Gasoline, and Lurgi gasification technologies. Three direct coal liquefaction processes were examined for product toxicity and air emissions: Solvent Refined Coal (I and II) and the Exxon Donor Solvent Process. Also described in the third section is an evaluation of environmental and health hazards associated with the use of synthetic fuels from indirect coal liquefaction, direct coal liquefaction, and shale oil. Finally, the fourth section discusses some problems associated with performing, on a contractual basis, scientific and technical evaluations in support of U.S. EPA regulatory and research decisions.

  8. Acute aquatic toxicity of biodiesel fuels

    SciTech Connect (OSTI)

    Wright, B.; Haws, R.; Little, D.; Reese, D.; Peterson, C.; Moeller, G.

    1995-12-31

    This study develops data on the acute aquatic toxicity of selected biodiesel fuels which may become subject to environmental effects test regulations under the US Toxic Substances Control Act (TSCA). The test substances are Rape Methyl Ester (RME), Rape Ethyl Ester (REE), Methyl Soyate (MS), a biodiesel mixture of 20% REE and 80% Diesel, a biodiesel mixture of 50% REE and diesel, and a reference substance of Phillips D-2 Reference Diesel. The test procedure follows the Daphnid Acute Toxicity Test outlined in 40 CFR {section} 797.1300 of the TSCA regulations. Daphnia Magna are exposed to the test substance in a flow-through system consisting of a mixing chamber, a proportional diluter, and duplicate test chambers. Novel system modifications are described that accommodate the testing of oil-based test substances with Daphnia. The acute aquatic toxicity is estimated by an EC50, an effective concentration producing immobility in 50% of the test specimen.

  9. Surviving the toxics in south Louisiana: A minority perspective

    SciTech Connect (OSTI)

    Wright, B.

    1995-12-01

    The Louisiana industrial corridor along the Mississippi River is lined with 136 petro-chemical plants and serves oil refineries. This approximates nearly one plant or refinery for every half mile of the river. The air, ground, and water along this corridor are so full or carcinogens that it has been described as a massive human experiment. Poor blacks live in river towns near the brunt of this discharge. Total mortality rates and cancer mortality rates in counties along the Mississippi River are significantly higher than in the rest of the nation`s counties. Moreover, the areas of greatest toxic discharge. Findings of disproportionately high mortality rates along the Mississippi, especially in communities on the lower river where toxic discharge minority and poor communities along the Mississippi River chemical corridor.

  10. Assessing the toxic effects of ethylene glycol ethers using Quantitative Structure Toxicity Relationship models

    SciTech Connect (OSTI)

    Ruiz, Patricia; Mumtaz, Moiz; Gombar, Vijay

    2011-07-15

    Experimental determination of toxicity profiles consumes a great deal of time, money, and other resources. Consequently, businesses, societies, and regulators strive for reliable alternatives such as Quantitative Structure Toxicity Relationship (QSTR) models to fill gaps in toxicity profiles of compounds of concern to human health. The use of glycol ethers and their health effects have recently attracted the attention of international organizations such as the World Health Organization (WHO). The board members of Concise International Chemical Assessment Documents (CICAD) recently identified inadequate testing as well as gaps in toxicity profiles of ethylene glycol mono-n-alkyl ethers (EGEs). The CICAD board requested the ATSDR Computational Toxicology and Methods Development Laboratory to conduct QSTR assessments of certain specific toxicity endpoints for these chemicals. In order to evaluate the potential health effects of EGEs, CICAD proposed a critical QSTR analysis of the mutagenicity, carcinogenicity, and developmental effects of EGEs and other selected chemicals. We report here results of the application of QSTRs to assess rodent carcinogenicity, mutagenicity, and developmental toxicity of four EGEs: 2-methoxyethanol, 2-ethoxyethanol, 2-propoxyethanol, and 2-butoxyethanol and their metabolites. Neither mutagenicity nor carcinogenicity is indicated for the parent compounds, but these compounds are predicted to be developmental toxicants. The predicted toxicity effects were subjected to reverse QSTR (rQSTR) analysis to identify structural attributes that may be the main drivers of the developmental toxicity potential of these compounds.

  11. Case history of a toxicity identification/reduction evaluation (TI/RE) at a petroleum refinery

    SciTech Connect (OSTI)

    Arnold, W.R.; Zaleski, R.T.; Biddinger, G.R.; Simmerman, J.J.; Stewart, J.D.

    1994-12-31

    During an operational turn-around at a high conversion petroleum refinery, the final wastewater effluent became toxic to three fish species used in continuous on-line flow-through acute toxicity tests. Discharge of effluent to the receiving bay was promptly halted. Wastewater treatment continued and the treated effluent was diverted to a series of holding ponds with limited capacity. A refinery team was formed to coordinate toxicity identification studies as well as to facilitate modifications of waste disposal practices and treatment operations. A test program was conducted, consisting of one rainbow trout Phase 1 TIE and 84 strategic acute toxicity tests. As a result, a treatment methodology was identified within three days and within eight days of first observing toxicity a cationic water treatment polymer was identified as the primary toxicant. The toxicity was due to increased bioavailability of the polymer when suspended solids loads dropped during turn-around. Use of the polymer was immediately stopped and discharge to the bay was resumed with 100% survival of all three monitoring species. The authors present an overview of the studies and decisions leading to the successful identification and management of this situation.

  12. Effects of water hardness on the toxicity of manganese to developing brown trout (Salmo trutta)

    SciTech Connect (OSTI)

    Stubblefield, W.A.; Garrison, T.D.; Hockett, J.R.; Brinkman, S.F.; Davies, P.H.; McIntyre, M.W.

    1997-10-01

    Manganese is a common constituent of point and nonpoint discharges from mining and smelting activities. Available data indicate that Mn is acutely toxic at relatively high aqueous concentrations, when compared with trace metals, and its toxicity is affected by water hardness. Little information is available regarding the chronic toxicity of manganese. Early-life-stage (ELS) tests were conducted to determine the toxicity of manganese to brown trout (Salmo trutta) and to evaluate the extent to which water hardness (ranging from 30 to 450 mg/L as CaCO{sub 3}) affects the chronic toxicity of Mn. Water hardness of significantly affected Mn chronic toxicity, with toxicity decreasing with increasing hardness. Decreased survival was the predominant effect noted in the 30-mg/L hardness experiment, while significant effects on growth (as measured by changes in body weight) were observed in both the 150- and 450-mg/L hardness experiments. Twenty-five percent inhibition concentration (IC25) values, based on the combined endpoints (i.e., survival and body weight), were 4.67, 5.59, and 8.68 mg Mn/L (based on measured Mn concentration) at hardness levels of approximately 30, 150, and 450 mg/L as CaCO{sub 3}, respectively.

  13. Hazard index for underground toxic material

    SciTech Connect (OSTI)

    Smith, C.F.; Cohen, J.J.; McKone, T.E.

    1980-06-01

    To adequately define the problem of waste management, quantitative measures of hazard must be used. This study reviews past work in the area of hazard indices and proposes a geotoxicity hazard index for use in characterizing the hazard of toxic material buried underground. Factors included in this index are: an intrinsic toxicity factor, formulated as the volume of water required for dilution to public drinking-water levels; a persistence factor to characterize the longevity of the material, ranging from unity for stable materials to smaller values for shorter-lived materials; an availability factor that relates the transport potential for the particular material to a reference value for its naturally occurring analog; and a correction factor to accommodate the buildup of decay progeny, resulting in increased toxicity.

  14. DOE contractor's meeting on chemical toxicity

    SciTech Connect (OSTI)

    Not Available

    1987-01-01

    The Office of Health and Environmental Research (OHER) is required to determine the potential health and environmental effects associated with energy production and use. To ensure appropriate communication among investigators and scientific disciplines that these research studies represent, OHER has sponsored workshops. This document provides a compilation of activities at the Third Annual DOE/OHER Workshop. This year's workshop was broadened to include all OHER activities identified as within the chemical effects area. The workshop consisted of eight sessions entitled Isolation and Detection of Toxic chemicals; Adduct Formation and Repair; Chemical Toxicity (Posters); Metabolism and Genotoxicity; Inhalation Toxicology; Gene Regulation; Metals Toxicity; and Biological Mechanisms. This document contains abstracts of the information presented by session.

  15. Acute inhalation toxicity of carbonyl sulfide

    SciTech Connect (OSTI)

    Benson, J.M.; Hahn, F.F.; Barr, E.B. [and others

    1995-12-01

    Carbonyl sulfide (COS), a colorless gas, is a side product of industrial procedures sure as coal hydrogenation and gasification. It is structurally related to and is a metabolite of carbon disulfide. COS is metabolized in the body by carbonic anhydrase to hydrogen sulfide (H{sub 2}S), which is thought to be responsible for COS toxicity. No threshold limit value for COS has been established. Results of these studies indicate COS (with an LC{sub 50} of 590 ppm) is slightly less acutely toxic than H{sub 2}S (LC{sub 50} of 440 ppm).

  16. Predictive Factors for Acute and Late Urinary Toxicity After Permanent Prostate Brachytherapy: Long-Term Outcome in 712 Consecutive Patients

    SciTech Connect (OSTI)

    Keyes, Mira Miller, Stacy; Moravan, Veronika; Pickles, Tom; McKenzie, Michael; Pai, Howard; Liu, Mitchell; Kwan, Winkle; Agranovich, Alexander; Spadinger, Ingrid; Lapointe, Vincent; Halperin, Ross; Morris, W. James

    2009-03-15

    Purpose: To describe the frequency of acute and late Radiation Therapy Oncology Group (RTOG) urinary toxicity, associated predictive factors, and resolution of International Prostate Symptom Score (IPSS) in 712 consecutive prostate brachytherapy patients. Methods and Materials: Patients underwent implantation between 1998 and 2003 (median follow-up, 57 months). The IPSS and RTOG toxicity data were prospectively collected. The patient, treatment, and implant factors were examined for an association with urinary toxicity. The time to IPSS resolution was examined using Kaplan-Meier curves, and multivariate modeling of IPSS resolution was done using Cox proportional hazards regression analysis. Logistic regression analysis was used to examine the factors associated with urinary toxicity. Results: The IPSS returned to baseline at a median of 12.6 months. On multivariate analysis, patients with a high baseline IPSS had a quicker resolution of their IPSS. Higher prostate D90 (dose covering 90% of the prostate), maximal postimplant IPSS, and urinary retention slowed the IPSS resolution time. The rate of the actuarial 5-year late urinary (>12 months) RTOG Grade 0, 1, 2, 3, and 4 was 32%, 36%, 24%, 6.2%, and 0.1%, respectively. At 7 years, the prevalence of RTOG Grade 0-1 was 92.5%. Patients with a larger prostate volume, greater number of needles, greater baseline IPSS, and use of hormonal therapy had more acute toxicity. On multivariate analysis, the significant predictors for late greater than or equal to RTOG toxicity 2 were a greater baseline IPSS, maximal postimplant IPSS, presence of acute toxicity, and higher prostate V150 (volume of the prostate covered by 150% of the dose). More recently implanted patients had less acute urinary toxicity and patients given hormonal therapy had less late urinary toxicity (all p < 0.02). Conclusion: Most urinary symptoms resolved within 12 months after prostate brachytherapy, and significant long-term urinary toxicity was very low

  17. Causes of toxicity in stormwater runoff from sawmills

    SciTech Connect (OSTI)

    Bailey, H.C.; Elphick, J.R.; Potter, A.; Chao, E.; Konasewich, D.; Zak, J.B.

    1999-07-01

    Samples of stormwater runoff from nine sawmills in British Columbia, Canada, were tested for acute toxicity with juvenile rainbow trout over a 23-month period. Forty-two of the 58 samples tested exhibited toxicity. Causes of toxicity were investigated using toxicity identification evaluation techniques. Toxicity was attributed to divalent cations, particularly zinc, in 32 of the samples. The low hardness associated with most of the samples increased the potential for metal toxicity. For example, the LC50 of zinc was 14 {micro}g/L at a hardness of 5 mg/L. Toxicity in the remaining samples was largely attributed to tannins and lignins and was associated with areas of bulk log handling. No evidence was found to indicate that antisapstain chemicals applied to freshly cut wood contributed to toxicity.

  18. Toxicity Data to Determine Refrigerant Concentration Limits

    SciTech Connect (OSTI)

    Calm, James M.

    2000-09-30

    This report reviews toxicity data, identifies sources for them, and presents resulting exposure limits for refrigerants for consideration by qualified parties in developing safety guides, standards, codes, and regulations. It outlines a method to calculate an acute toxicity exposure limit (ATEL) and from it a recommended refrigerant concentration limit (RCL) for emergency exposures. The report focuses on acute toxicity with particular attention to lethality, cardiac sensitization, anesthetic and central nervous system effects, and other escape-impairing effects. It addresses R-11, R-12, R-22, R-23, R-113, R-114, R-116, R-123, R-124, R-125, R-134, R-134a, R-E134, R-141b, R-142b, R-143a, R-152a, R-218, R-227ea, R-236fa, R-245ca, R-245fa, R-290, R-500, R-502, R-600a, R-717, and R-744. It summarizes additional data for R-14, R-115, R-170 (ethane), R-C318, R-600 (n-butane), and R-1270 (propylene) to enable calculation of limits for blends incorporating them. The report summarizes the data a nd related safety information, including classifications and flammability data. It also presents a series of tables with proposed ATEL and RCL concentrations-in dimensionless form and the latter also in both metric (SI) and inch-pound (IP) units of measure-for both the cited refrigerants and 66 zerotropic and azeotropic blends. They include common refrigerants, such as R-404A, R-407C, R-410A, and R-507A, as well as others in commercial or developmental status. Appendices provide profiles for the cited single-compound refrigerants and for R-500 and R-502 as well as narrative toxicity summaries for common refrigerants. The report includes an extensive set of references.

  19. Hydrogen and Gaseous Fuel Safety and Toxicity

    SciTech Connect (OSTI)

    Lee C. Cadwallader; J. Sephen Herring

    2007-06-01

    Non-traditional motor fuels are receiving increased attention and use. This paper examines the safety of three alternative gaseous fuels plus gasoline and the advantages and disadvantages of each. The gaseous fuels are hydrogen, methane (natural gas), and propane. Qualitatively, the overall risks of the four fuels should be close. Gasoline is the most toxic. For small leaks, hydrogen has the highest ignition probability and the gaseous fuels have the highest risk of a burning jet or cloud.

  20. Toxic release inventory, (TRI), 1991. Data file

    SciTech Connect (OSTI)

    1991-12-31

    Section 313 of the Emergency Planning and Community Right-to-Know Act (also known as Title III) of the Superfund Amendments and Reauthorization Act of 1986 (Public Law 99-499) requires EPA to establish a national inventory of toxic chemical emissions from certain facilities. The final Toxic Chemical Release Form R and regulations for the 1987 reporting year were published in the Federal Register on February 16, 1988 (53 FR 4500-4554). The reporting requirement applies to owners and operators of facilities that have 10 or more full-time employees, that are in Standard Industrial Classification (SIC) codes 20 through 39 (i.e., manufacturing facilities) and that manufacture (including importing), process or otherwise use a listed toxic chemical in excess of specified threshold quantities. The law mandates that the data be made publicly available through a computer database. The online TRI file should appeal to a broad-based user audience including industry, state and local environmental agencies, emergency planning committees, the Federal Government and other regulatory groups.

  1. Toxicity of materials used in the manufacture of lithium batteries

    SciTech Connect (OSTI)

    Archuleta, M.M.

    1994-05-01

    The growing interest in battery systems has led to major advances in high-energy and/or high-power-density lithium batteries. Potential applications for lithium batteries include radio transceivers, portable electronic instrumentation, emergency locator transmitters, night vision devices, human implantable devices, as well as uses in the aerospace and defense programs. With this new technology comes the use of new solvent and electrolyte systems in the research, development, and production of lithium batteries. The goal is to enhance lithium battery technology with the use of non-hazardous materials. Therefore, the toxicity and health hazards associated with exposure to the solvents and electrolytes used in current lithium battery research and development is evaluated and described.

  2. Update On Aquatic Toxicity/Whole Effluent Toxicity (WET) Issues, 2005

    SciTech Connect (OSTI)

    Specht, Winona L

    2005-07-01

    This paper summarizes recent changes in the field of aquatic toxicity/Whole Effluent Toxicity (WET) testing. There are been numerous legal challenges to the validity of WET testing, both at the federal and state levels, but to date, the regulators have prevailed and WET testing is used as a regulatory tool to ensure that the biota of receiving streams are protected. The most recent ruling at the federal level was on December 10, 2004, when a federal appeals court in the District of Columbia upheld the validity of WET testing. At the state level, at the urging of the South Carolina Manufacturers Alliance, the state legislature passed a law (the South Carolina Aquatic Life Protection Act) in 2004 that requires the South Carolina Department of Health and Environmental Control (DHEC) to evaluate the accuracy and precision of the WET test. As a result, SCDHEC removed WET test limits from several NPDES permits. EPA took issue with the impact of the legislation and SCDHEC's actions, and as a result, EPA has taken over several NPDES permits from SCDHEC and threatened to revoke the state's delegated NPDES permit program. A new Act was signed into law in March 2005, which does not exclude the use of chronic toxicity testing for regulatory compliance. As a result, EPA has turned over the issuance of NPDES permits back to SCDHEC. In December 2004, the U.S. EPA issued the Draft National WET Implementation Guidance document for review and comment. The guidance contains recommendations on the determination of ''reasonable potential'' for toxicity. The EPA's ECOTOX database is a valuable resource of toxicity data for many chemicals. For those cases in which there are no toxicity data or very limited data available, the EPA has developed two models, the Interspecies Correlation Estimation (ICE) and the Acute to Chronic Estimation (ACE), for predicting toxicity. Active areas of research include assessing the uptake of heavy metals via multiple routes of exposure, the development of

  3. Toxicity of contaminants in lagoons and pannes of the Indiana Dunes National Lakeshore

    SciTech Connect (OSTI)

    Gillespie, R.; Speelman, J. [Indiana Univ.-Purdue Univ., Fort Wayne, IN (United States); Stewart, P.M. [National Biological Service, Porter, IN (United States). Indiana Dunes National Lakeshore

    1995-12-31

    Contaminants in water and sediments of lagoons and pannes were 2--90 times greater at sites adjacent to slag and coal piles than those at reference sites. One site (Lagoon-US5) had sediments with very high concentrations of toxic organics (e.g. naphthalene, phenanthrene, dibenzofuran). Although analyses indicated a gradient of contaminant concentration with distance from their sources, toxicity assays were somewhat equivocal. With the exception of less reproduction in Ceriodaphnia at one lagoon site (US3 = 0.55 of reference), survival of fathead minnows and reproduction in Ceriodaphnia in lagoon and panne waters varied independently of the contaminant concentration. In fact, there was better Ceriodaphnia reproduction in water from two contaminated sites (Lagoon-US5, Panne-WP1) than in water from reference sites. Fathead minnow survival, Ceriodaphnia survival, Ceriodaphnia reproduction, amphipod survival, and amphipod growth varied among sites in toxicity assays with sediments, 100% mortality of fatheads at Lagoon-US5, 100% mortality of Ceriodaphnia at Lagoon-US3, and less survival of fathead minnows at Lagoon-US3 indicate possible toxicity from contaminants in sediments at these sites. Of all organisms and end-points tested, Ceriodaphnia survival seemed to be most closely associated with concentrations of contaminants in lagoon water and sediments. Amphipod survival also varied with contaminants in sediments, however, survival in sediments of contaminated sites ranged only from 0.90--0.93 of reference sites. Although the results are not consistent among organisms, toxicity assays indicate that sediments from the lagoon site with the highest contaminants (Lagoon-US5) and possibly those from another contaminated lagoon site (Lagoon-US3) could be toxic to aquatic organisms. Water and sediments from contaminated panne sites do not appear to be toxic to aquatic test organisms.

  4. Yellow phosphorus process to convert toxic chemicals to non-toxic products

    DOE Patents [OSTI]

    Chang, S.G.

    1994-07-26

    The present invention relates to a process for generating reactive species for destroying toxic chemicals. This process first contacts air or oxygen with aqueous emulsions of molten yellow phosphorus. This contact results in rapid production of abundant reactive species such as O, O[sub 3], PO, PO[sub 2], etc. A gaseous or liquid aqueous solution organic or inorganic chemicals is next contacted by these reactive species to reduce the concentration of toxic chemical and result in a non-toxic product. The final oxidation product of yellow phosphorus is phosphoric acid of a quality which can be recovered for commercial use. A process is developed such that the byproduct, phosphoric acid, is obtained without contamination of toxic species in liquids treated. A gas stream containing ozone without contamination of phosphorus containing species is also obtained in a simple and cost-effective manner. This process is demonstrated to be effective for destroying many types of toxic organic, or inorganic, compounds, including polychlorinated biphenyls (PCB), aromatic chlorides, amines, alcohols, acids, nitro aromatics, aliphatic chlorides, polynuclear aromatic compounds (PAH), dyes, pesticides, sulfides, hydroxyamines, ureas, dithionates and the like. 20 figs.

  5. Yellow phosphorus process to convert toxic chemicals to non-toxic products

    DOE Patents [OSTI]

    Chang, Shih-Ger

    1994-01-01

    The present invention relates to a process for generating reactive species for destroying toxic chemicals. This process first contacts air or oxygen with aqueous emulsions of molten yellow phosphorus. This contact results in rapid production of abundant reactive species such as O, O.sub.3, PO, PO.sub.2, etc. A gaseous or liquid aqueous solution organic or inorganic chemicals is next contacted by these reactive species to reduce the concentration of toxic chemical and result in a non-toxic product. The final oxidation product of yellow phosphorus is phosphoric acid of a quality which can be recovered for commercial use. A process is developed such that the byproduct, phosphoric acid, is obtained without contamination of toxic species in liquids treated. A gas stream containing ozone without contamination of phosphorus containing species is also obtained in a simple and cost-effective manner. This process is demonstrated to be effective for destroying many types of toxic organic, or inorganic, compounds, including polychlorinated biphenyls (PCB), aromatic chlorides, amines, alcohols, acids, nitro aromatics, aliphatic chlorides, polynuclear aromatic compounds (PAH), dyes, pesticides, sulfides, hydroxyamines, ureas, dithionates and the like.

  6. Organic ligands reduce copper toxicity in Pseudomonas syringae

    SciTech Connect (OSTI)

    Azenha, M.; Vasconcelos, M.T.; Cabral, J.P.S.

    1995-03-01

    Pseudomonas syringae cells were exposed to 100 {mu}M copper alone, or to previously equilibrated copper sulfate-ligand solutions. Ligand concentrations were determined experimentally as those that reduced the free copper concentration to 5 {mu}M (determined with a Cu{sup 2+}-selective electrode). These values were in agreement with those calculated by computational equilibrium simulation based on published stability constants. Exposure of P. syringae cells to copper sulfate, chloride, or nitrate resulted in similar high mortality, suggesting that copper was responsible for cell death. Acetate, succinate, proline, lysine, cysteine, and EDTA significantly reduced both the amount of copper bound to the cells and cell death, indicating that not only strong chelating agents but also weak and moderate copper ligands can effectively antagonize copper toxicity. However, cysteine and EDTA were considerably more effective than acetate, succinate, proline, and lysine, indicating that copper toxicity is not simply a function of free copper concentration but depends on the nature of the ligand. The results suggested that a significant fraction of copper bound to acetate, succinate, proline, or lysine was displaced to the bacteria or, alternatively, mixed copper-ligand-cell complexes could be formed. On the contrary, none of these phenomena occurred for the copper complexes with cysteine or EDTA.

  7. Method and apparatus for diagnosis of lead toxicity

    DOE Patents [OSTI]

    Rosen, John F.; Slatkin, Daniel N.; Wielopolski, Lucian

    1989-01-01

    Improved methods and apparatus for in vivo measurement of the skeletal lead burden of a patient and for diagnosis of lead toxicity are disclosed. The apparatus comprises an x-ray tube emitting soft low energy x-rays from a silver anode, a polarizer for polarizing the emitted x-rays, and a detector for detecting photons fluoresced from atoms in the patient's tibia upon irradiation by the polarized x-rays. The fluoresced photons are spectrally analyzed to determine their energy distribution. Peaks indicating the presence of lead are identified if the patient has relatively high bone lead content. The data may be compared to data recorded with respect to a similar test performed on patients having also had the conventional EDTA chelation tests performed thereon in order to correlate the test results with respect to a particular patient to the conventionally accepted EDTA chelation test.

  8. Renewable, Non-Toxic and Cost Competitive Solvents and Plasticizers |

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Department of Energy Renewable, Non-Toxic and Cost Competitive Solvents and Plasticizers Renewable, Non-Toxic and Cost Competitive Solvents and Plasticizers Breakout Session 1-D: The Pitch Renewable, Non-Toxic and Cost Competitive Solvents and Plasticizers Len Rand, Chief Executive Officer, Chairman, xF Technologies rand_bioenergy_2015.pdf (874.76 KB) More Documents & Publications Vehicle Technologies Office Merit Review 2015: Development of Industrially Viable Battery Electrode Coatings

  9. Comparative Toxicity of Combined Particle and Semi-Volatile Organic

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Fractioins of Gasoline and Diesel Emissions | Department of Energy Toxicity of Combined Particle and Semi-Volatile Organic Fractioins of Gasoline and Diesel Emissions Comparative Toxicity of Combined Particle and Semi-Volatile Organic Fractioins of Gasoline and Diesel Emissions 2002 DEER Conference Presentation: Lovelace Respiratory Research Institute 2002_deer_mauderly.pdf (63 KB) More Documents & Publications Relationship Between Composition and Toxicity of Engine Emission Samples

  10. Relationship Between Composition and Toxicity of Engine Emission Samples |

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Department of Energy Emission Samples Relationship Between Composition and Toxicity of Engine Emission Samples 2003 DEER Conference Presentation: Lovelace Respiratory Research Institute 2003_deer_mauderly.pdf (71.75 KB) More Documents & Publications Lung Toxicity and Mutagenicity of Emissions From Heavy-Duty Compressed Natural Gas (CNG)-Powered Vehicles Comparative Toxicity of Combined Particle and Semi-Volatile Organic Fractioins of Gasoline and Diesel Emissions Relationship Between

  11. Toxic Substances Control Act Uranium Enrichment Federal Facilities...

    Office of Environmental Management (EM)

    Toxic Substance Control Act Uranium Enrichment Federal Facilities Compliance Agreement ... for bringing DOE's former and active Uranium Enrichment Plants in Paducah, Portsmouth, ...

  12. Early Proctoscopy is a Surrogate Endpoint of Late Rectal Toxicity...

    Office of Scientific and Technical Information (OSTI)

    Prostate Cancer Treated With Radiotherapy Citation Details In-Document Search Title: Early Proctoscopy is a Surrogate Endpoint of Late Rectal Toxicity in Prostate Cancer Treated ...

  13. Toxic Substances Control Act Uranium Enrichment Federal Facility...

    Office of Environmental Management (EM)

    Toxic Substances Control Act (TSCA) Uranium Enrichment Federal Facility Compliance Agreement establishes a plan to bring DOE's Uranium Enrichment Plants (and support facilities) ...

  14. Toxic chemical considerations for tank farm releases

    SciTech Connect (OSTI)

    Van Keuren, J.C.; Davis, J.S., Westinghouse Hanford

    1996-08-01

    This topical report contains technical information used to determine the accident consequences of releases of toxic chemical and gases for the Tank Farm Final Safety Analysis report (FSAR).It does not provide results for specific accident scenarios but does provide information for use in those calculations including chemicals to be considered, chemical concentrations, chemical limits and a method of summing the fractional contributions of each chemical. Tank farm composites evaluated were liquids and solids for double shell tanks, single shell tanks, all solids,all liquids, headspace gases, and 241-C-106 solids. Emergency response planning guidelines (ERPGs) were used as the limits.Where ERPGs were not available for the chemicals of interest, surrogate ERPGs were developed. Revision 2 includes updated sample data, an executive summary, and some editorial revisions.

  15. Evaluation of the effects of coal fly ash amendments on the toxicity of a contaminated marine sediment

    SciTech Connect (OSTI)

    Burgess, R.M.; Perron, M.M.; Friedman, C.L.; Suuberg, E.M.; Pennell, K.G.; Cantwell, M.G.; Pelletier, M.C.; Ho, K.T.; Serbst, J.R.; Ryba, S.A.

    2009-01-15

    Approaches for cleaning up contaminated sediments range from dredging to in situ treatment. In this study, we discuss the effects of amending reference and contaminated sediments with coal fly ash to reduce the bioavailability and toxicity of a field sediment contaminated with polycyclic aromatic hydrocarbons (PAHs). Six fly ashes and a coconut charcoal were evaluated in 7-d whole sediment toxicity tests with a marine amphipod (Ampelisca abdita) and mysid (Americamysis bahia). Fly ashes with high carbon content and the coconut charcoal showed proficiency at reducing toxicity. Some of the fly ashes demonstrated toxicity in the reference treatments. It is suspected that some of this toxicity is related to the presence of ammonia associated with fly ashes as a result of postoxidation treatment to reduce nitrous oxide emissions. Relatively simple methods exist to remove ammonia from fly ash before use, and fly ashes with low ammonia content are available. Fly ashes were also shown to effectively reduce overlying water concentrations of several PAHs. No evidence was seen of the release of the metals cadmium, copper, nickel, or lead from the fly ashes. A preliminary 28-d polychaete bioaccumulation study with one of the high-carbon fly ashes and a reference sediment was also performed. Although preliminary, no evidence was seen of adverse effects to worm growth or lipid content or of accumulation of PAHs or mercury from exposure to the fly ash. These data show fly ashes with high carbon content could represent viable remedial materials for reducing the bioavailability of organic contaminants in sediments.

  16. Process for removing toxicants from aqueous petroleum waste streams

    SciTech Connect (OSTI)

    O'Reilly, K.T.; Suzuki, J.P.

    1993-08-17

    A process is described for removing a toxicant from an aqueous waste stream associated with the production of petroleum or petroleum products wherein the toxicant is a thermally stable organic molecule having a molecular weight in the range from about 200 to about 400 and at least one carboxylic acid group, said toxicant further having a 96-hour median lethal concentration for larval rainbow trout and larval fathead minnows of less than about 10 ppb, said process comprising the steps of: (a) contacting the waste stream with an activated non-ionic macro reticular polymeric resin having low to intermediate surface polarity for a time sufficient to reduce the amount of said toxicant in said waste stream to a preselected level, and (b) recovering the waste stream from the resin with a reduced level of toxicity.

  17. Court decision dropping toxic substance rules stands

    SciTech Connect (OSTI)

    Bryant, C.R.

    1993-06-01

    In a somewhat surprising move, the U.S. Department of Labor has decided not to appeal a court decision essentially dropping regulations established by the Occupational Safety and Health Administration (OSHA) for about 400 hazardous substances. The decision leaves unregulated or subject to reduced standards substances that range from carbon monoxide to perchloroethylene. The Labor Department had until March 22, 1993, to appeal the court decision. On July 8, 1992, the U.S. Court of Appeals for the 11th Circuit overturned OSHA's final Air Contaminants Standard, which was promulgated in 1989. The standard established permissible exposure limits (PELs) for 428 toxic substances. In AFL-CIO vs. OSHA, the Court ruled that OSHA failed to make a separate scientific case for evaluating health risks of each chemical. Because of the decision not to appeal, PELs for more than half of the substances regulated by OSHA now are removed from the books or revert to the voluntary industry standards adopted by OSHA in 1970 and in force prior to the 1989 final rule.

  18. Acute aquatic toxicity and biodegradation potential of biodiesel fuels

    SciTech Connect (OSTI)

    Haws, R.A.; Zhang, X.; Marshall, E.A.; Reese, D.L.; Peterson, C.L.; Moeller, G.

    1995-12-31

    Recent studies on the biodegradation potential and aquatic toxicity of biodiesel fuels are reviewed. Biodegradation data were obtained using the shaker flask method observing the appearance of CO{sub 2} and by observing the disappearance of test substance with gas chromatography. Additional BOD{sub 5} and COD data were obtained. The results indicate the ready biodegradability of biodiesel fuels as well as the enhanced co-metabolic biodegradation of biodiesel and petroleum diesel fuel mixtures. The study examined reference diesel, neat soy oil, neat rape oil, and the methyl and ethyl esters of these vegetable oils as well as various fuel blends. Acute toxicity tests on biodiesel fuels and blends were performed using Oncorhynchus mykiss (Rainbow Trout) in a static non-renewal system and in a proportional dilution flow replacement system. The study is intended to develop data on the acute aquatic toxicity of biodiesel fuels and blends under US EPA Good Laboratory Practice Standards. The test procedure is designed from the guidelines outlined in Methods for Measuring the Acute Toxicity of Effluents and Receiving Waters to Freshwater and Marine Organisms and the Fish Acute Aquatic Toxicity Test guideline used to develop aquatic toxicity data for substances subject to environmental effects test regulations under TSCA. The acute aquatic toxicity is estimated by an LC50, a lethal concentration effecting mortality in 50% of the test population.

  19. Physicochemical properties and toxicities of hydrophobicpiperidinium and pyrrolidinium ionic liquids

    SciTech Connect (OSTI)

    Salminen, Justin; Papaiconomou, Nicolas; Kumar, R. Anand; Lee,Jong-Min; Kerr, John; Newman, John; Prausnitz, John M.

    2007-06-25

    Some properties are reported for hydrophobic ionic liquids (IL) containing 1-methyl-1-propyl pyrrolidinium [MPPyrro]{sup +}, 1-methyl-1-butyl pyrrolidinium [MBPyrro]{sup +}, 1-methyl-1-propyl piperidinium [MPPip]{sup +}, 1-methyl-1-butyl piperidinium [MBPip]{sup +}, 1-methyl-1-octylpyrrolidinium [MOPyrro]{sup +} and 1-methyl-1-octylpiperidinium [MOPip]{sup +} cations. These liquids provide new alternatives to pyridinium and imidazolium ILs. High thermal stability of an ionic liquid increases safety in applications like rechargeable lithium-ion batteries and other electrochemical devices. Thermal properties, ionic conductivities, viscosities, and mutual solubilities with water are reported. In addition, toxicities of selected ionic liquids have been measured using a human cancer cell-line. The ILs studied here are sparingly soluble in water but hygroscopic. We show some structure-property relationships that may help to design green solvents for specific applications. While ionic liquids are claimed to be environmentally-benign solvents, as yet few data have been published to support these claims.

  20. Toxic Substances Control Act Uranium Enrichment Federal Facilities...

    Office of Environmental Management (EM)

    Thomas L. McCall, Jr. http:www.em.doe.govffaaortsca.html 4252001 Toxic Substances Control Act Uranium Enrichment Federal Facilities Compliance Agree.. Page 12 of 26 Deputy ...

  1. Toxic Chemical Release Inventory reporting ``Qs & As``. Environmental Guidance

    SciTech Connect (OSTI)

    Not Available

    1994-03-01

    This document offers guidance on toxic chemical release inventory reporting, pursuant to Section 313 of the Emergency Planning and Community Right-to-Know Act (EPCRA) at DOE sites.

  2. Oxidative stress-induced autophagy: Role in pulmonary toxicity

    SciTech Connect (OSTI)

    Malaviya, Rama; Laskin, Jeffrey D.; Laskin, Debra L.

    2014-03-01

    Autophagy is an evolutionarily conserved catabolic process important in regulating the turnover of essential proteins and in elimination of damaged organelles and protein aggregates. Autophagy is observed in the lung in response to oxidative stress generated as a consequence of exposure to environmental toxicants. Whether autophagy plays role in promoting cell survival or cytotoxicity is unclear. In this article recent findings on oxidative stress-induced autophagy in the lung are reviewed; potential mechanisms initiating autophagy are also discussed. A better understanding of autophagy and its role in pulmonary toxicity may lead to the development of new strategies to treat lung injury associated with oxidative stress. - Highlights: • Exposure to pulmonary toxicants is associated with oxidative stress. • Oxidative stress is known to induce autophagy. • Autophagy is upregulated in the lung following exposure to pulmonary toxicants. • Autophagy may be protective or pathogenic.

  3. Toxic Substances Control Act Uranium Enrichment Federal Facilities...

    Office of Environmental Management (EM)

    Thomas L. McCall, Jr. http:www.em.doe.govffaaortsca.html 4252001 Toxic Substances Control Act Uranium Enrichment Federal Facilities Compliance Agree.. Page 12 of 26 Deputy...

  4. Multiple Species of Bacteria Convert Elemental Mercury to Toxic...

    Office of Science (SC) Website

    Researchers are studying how bacteria transform mercury into a toxic form in the environment that can accumulate in the food web, posing a threat to wildlife and people. The ...

  5. Nano/bio treatment of polychlorinated biphenyls with evaluation of comparative toxicity

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Le, Thao Thanh; Francis, Arokiasamy J.; Nguyen, Hoang Khanh; Jeon, Jong -Rok; Chang, Yoon -Seok

    2015-02-03

    The persistence of polychlorinated biphenyl (PCB) Aroclor 1248 in soils and sediments is a major concern because of its toxicity and presence at high concentrations. In this study, we developed an integrated remediation system for PCBs using chemical catalysis and biodegradation. The dechlorination of Aroclor 1248 was achieved by treatment with bimetallic nanoparticles Pd/nFe under anoxic conditions. Among the 32 PCB congeners of Aroclor 1248 examined, our process dechlorinated 99%, 92%, 84%, and 28% of tri-, tetra-, penta-, and hexachlorinated biphenyls, respectively. The resulting biphenyl was biodegraded rapidly by Burkholderia xenovorans LB400. Benzoic acid was detected as an intermediate duringmore » the biodegradation process. The toxicity of the residual PCBs after nano-bio treatment was evaluated in terms of toxic equivalent values which decreased from 33.8 × 10-5 μg g-1 to 9.5 × 10-5 μg g-1. The residual PCBs also had low cytotoxicity toward Escherichia coli as demonstrated by lower reactive oxygen species levels, lower glutathione peroxidase activity, and a reduced number of dead bacteria.« less

  6. Nano/bio treatment of polychlorinated biphenyls with evaluation of comparative toxicity

    SciTech Connect (OSTI)

    Le, Thao Thanh; Francis, Arokiasamy J.; Nguyen, Hoang Khanh; Jeon, Jong -Rok; Chang, Yoon -Seok

    2015-02-03

    The persistence of polychlorinated biphenyl (PCB) Aroclor 1248 in soils and sediments is a major concern because of its toxicity and presence at high concentrations. In this study, we developed an integrated remediation system for PCBs using chemical catalysis and biodegradation. The dechlorination of Aroclor 1248 was achieved by treatment with bimetallic nanoparticles Pd/nFe under anoxic conditions. Among the 32 PCB congeners of Aroclor 1248 examined, our process dechlorinated 99%, 92%, 84%, and 28% of tri-, tetra-, penta-, and hexachlorinated biphenyls, respectively. The resulting biphenyl was biodegraded rapidly by Burkholderia xenovorans LB400. Benzoic acid was detected as an intermediate during the biodegradation process. The toxicity of the residual PCBs after nano-bio treatment was evaluated in terms of toxic equivalent values which decreased from 33.8 × 10-5 μg g-1 to 9.5 × 10-5 μg g-1. The residual PCBs also had low cytotoxicity toward Escherichia coli as demonstrated by lower reactive oxygen species levels, lower glutathione peroxidase activity, and a reduced number of dead bacteria.

  7. Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity

    SciTech Connect (OSTI)

    Rashedinia, Marzieh; Lari, Parisa; Abnous, Khalil; Hosseinzadeh, Hossein

    2013-10-01

    Acrolein, a member of reactive ?,?-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3 mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including ?-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders. - Highlights: Acrolein intoxication increased lipid peroxidation and deplete GSH in rat brain. Effect of acrolein on protein levels of cerebral cortex was analyzed by 2DE-PAGE. Levels of a number of proteins with different biological functions were increased.

  8. Experimental study of toxic metal-sorbent reactions in a bench scale combustor

    SciTech Connect (OSTI)

    Owens, T.M.; Biswas, P.

    1996-11-01

    Toxic metals may enter a combustion chamber in many physical or chemical forms, for example, as a constituent of a hazardous or municipal solid waste to be incinerated or as a trace quantity in coal. Control of toxic metal emissions from combustors is currently being stipulated by the US EPA in the form of maximum achievable control technologies (MACT) for 11 metals and their compounds under Title 3 of the 1990 Clean Air Amendments. Several researchers have proposed using bulk solid sorbents in several geometries (packed bed, fluidized bed, and dry sorbent injection) and have demonstrated the potential to effectively remove metals form an air stream by means of chemisorption. In this paper the authors compare the use of a vapor phase silica precursor with a calcium precursor for lead capture in a high temperature flow reactor. The use of vapor phase sorbent precursors has the potential for more effective sorbent utilization. In a real system, the vapor phase sorbent precursors would be injected into the combustor where the precursor would first decompose, then be oxidized to form an aerosol in the high temperature environment, and provide a surface onto which metal compound vapors condense. Calcium-based sorbents are used in capturing sulfur compounds from coal combustion effluent gases but their effectiveness in chemisorbing toxic metals has not been studied extensively. The objective of this work is to show how the sorbent precursor addition affects the outlet metal aerosol`s chemical composition and size distribution. Specifically, the reactions and interactions that result when a vapor phase silica precursor, hexamethyl disiloxane, or a calcium precursor, calcium acetate, is inlet into a high temperature flow reactor along with an organic lead compound are investigated.

  9. Survey of toxicity and carcinogenity of mineral deposits

    SciTech Connect (OSTI)

    Furst, A.; Harding-Barlow, I.

    1981-11-03

    The toxicities and biogeochemical cycles of arsenic, cadmium, chromium, lead and nickel are reviewed in some detail, and other trace elements briefly mentioned. These heavy metals are used as a framework within which the problem of low-level radioactive waste disposal can be compared. (ACR)

  10. Duodenal Toxicity After Fractionated Chemoradiation for Unresectable Pancreatic Cancer

    SciTech Connect (OSTI)

    Kelly, Patrick; Das, Prajnan; Pinnix, Chelsea C.; Beddar, Sam; Briere, Tina; Pham, Mary; Krishnan, Sunil; Delclos, Marc E.; Crane, Christopher H.

    2013-03-01

    Purpose: Improving local control is critical to improving survival and quality of life for patients with locally advanced unresectable pancreatic cancer (LAPC). However, previous attempts at radiation dose escalation have been limited by duodenal toxicity. In order to guide future studies, we analyzed the clinical and dosimetric factors associated with duodenal toxicity in patients undergoing fractionated chemoradiation for LAPC. Methods and Materials: Medical records and treatment plans of 106 patients with LAPC who were treated with chemoradiation between July 2005 and June 2010 at our institution were reviewed. All patients received neoadjuvant and concurrent chemotherapy. Seventy-eight patients were treated with conventional radiation to 50.4 Gy in 28 fractions; 28 patients received dose-escalated radiation therapy (range, 57.5-75.4 Gy in 28-39 fractions). Treatment-related toxicity was graded according to Common Terminology Criteria for Adverse Events, version 4.0. Univariate and multivariate analyses were performed to assess prognostic influence of clinical, pathologic, and treatment-related factors by using Kaplan-Meier and Cox regression methods. Results: Twenty patients had treatment-related duodenal toxicity events, such as duodenal inflammation, ulceration, and bleeding. Four patients had grade 1 events, 8 had grade 2, 6 had grade 3, 1 had grade 4, and 1 had grade 5. On univariate analysis, a toxicity grade ≥2 was associated with tumor location, low platelet count, an absolute volume (cm{sup 3}) receiving a dose of at least 55 Gy (V{sub 55} {sub Gy} > 1 cm{sup 3}), and a maximum point dose >60 Gy. Of these factors, only V{sub 55} {sub Gy} ≥1 cm{sup 3} was associated with duodenal toxicity on multivariate analysis (hazard ratio, 6.7; range, 2.0-18.8; P=.002). Conclusions: This study demonstrates that a duodenal V{sub 55} {sub Gy} >1 cm{sup 3} is an important dosimetric predictor of grade 2 or greater duodenal toxicity and establishes it as a

  11. Advanced regenerative thermal oxidation (RTO) technology for air toxics control - selected case histories

    SciTech Connect (OSTI)

    Seiwert, J.J. Jr.

    1997-12-31

    Advanced design regenerative thermal oxidation (RTO) systems have been developed and are in commercial scale use for control of process emissions containing air toxics (HAPs) and VOCs. High operating temperatures coupled with high thermal energy recovery efficiencies inherent with RTO technology provide for high destruction efficiencies while minimizing formation of objectionable combustion byproducts. These results are achieved with low system operating costs. This paper covers development of advanced design commercial RTO systems for control of air emissions from several important commercial processes: total reduced sulfur (TRS) and other HAPs/VOC emissions from pulp mill processes. Chlorinated organics and other HAPs/VOC emissions from pharmaceutical manufacturing operations. The data presented represent the first commercial scale application of RTO technology to abate emissions from these processes. Particular design features required for each specific process, in order to provide reliable, safe and effective systems, are reviewed. Emissions abatement performance, as well as operational data, are presented for the systems.

  12. A vast collection of microbial genes that are toxic to bacteria...

    Office of Scientific and Technical Information (OSTI)

    A vast collection of microbial genes that are toxic to bacteria Citation Details In-Document Search Title: A vast collection of microbial genes that are toxic to bacteria In the ...

  13. SU-E-J-149: Establishing the Relationship Between Pre-Treatment Lung Ventilation, Dose, and Toxicity Outcome

    SciTech Connect (OSTI)

    Mistry, N; D'Souza, W; Sornsen de Koste, J; Senan, S

    2014-06-01

    Purpose: Recently, there has been an interest in incorporating functional information in treatment planning especially in thoracic tumors. The rationale is that healthy lung regions need to be spared from radiation if possible to help achieve better control on toxicity. However, it is still unclear whether high functioning regions need to be spared or have more capacity to deal with the excessive radiation as compared to the compromised regions of the lung. Our goal with this work is to establish the tools by which we can establish a relationship between pre-treatment lung function, dose, and radiographic outcomes of lung toxicity. Methods: Treatment planning was performed using a single phase of a 4DCT scan, and follow-up anatomical CT scans were performed every 3 months for most patients. In this study, we developed the pipeline of tools needed to analyze such a large dataset, while trying to establish a relationship between function, dose, and outcome. Pre-treatment lung function was evaluated using a recently published technique that evaluates Fractional Regional Ventilation (FRV). All images including the FRV map and the individual follow-up anatomical CT images were all spatially matched to the planning CT using a diffusion based Demons image registration algorithm. Change in HU value was used as a metric to capture the effects of lung toxicity. To validate the findings, a radiologist evaluated the follow-up anatomical CT images and scored lung toxicity. Results: Initial experience in 1 patient shows a relationship between the pre-treatment lung function, dose and toxicity outcome. The results are also correlated to the findings by the radiologist who was blinded to the analysis or dose. Conclusion: The pipeline we have established to study this enables future studies in large retrospective studies. However, the tools are dependent on the fidelity of 4DCT reconstruction for accurate evaluation of regional ventilation. Patent Pending for the technique

  14. Reliability of Quantitative Ultrasonic Assessment of Normal-Tissue Toxicity in Breast Cancer Radiotherapy

    SciTech Connect (OSTI)

    Yoshida, Emi J.; Chen Hao; Torres, Mylin; Andic, Fundagul; Liu Haoyang; Chen Zhengjia; Sun, Xiaoyan; Curran, Walter J.; Liu Tian

    2012-02-01

    Purpose: We have recently reported that ultrasound imaging, together with ultrasound tissue characterization (UTC), can provide quantitative assessment of radiation-induced normal-tissue toxicity. This study's purpose is to evaluate the reliability of our quantitative ultrasound technology in assessing acute and late normal-tissue toxicity in breast cancer radiotherapy. Method and Materials: Our ultrasound technique analyzes radiofrequency echo signals and provides quantitative measures of dermal, hypodermal, and glandular tissue toxicities. To facilitate easy clinical implementation, we further refined this technique by developing a semiautomatic ultrasound-based toxicity assessment tool (UBTAT). Seventy-two ultrasound studies of 26 patients (720 images) were analyzed. Images of 8 patients were evaluated for acute toxicity (<6 months postradiotherapy) and those of 18 patients were evaluated for late toxicity ({>=}6 months postradiotherapy). All patients were treated according to a standard radiotherapy protocol. To assess intraobserver reliability, one observer analyzed 720 images in UBTAT and then repeated the analysis 3 months later. To assess interobserver reliability, three observers (two radiation oncologists and one ultrasound expert) each analyzed 720 images in UBTAT. An intraclass correlation coefficient (ICC) was used to evaluate intra- and interobserver reliability. Ultrasound assessment and clinical evaluation were also compared. Results: Intraobserver ICC was 0.89 for dermal toxicity, 0.74 for hypodermal toxicity, and 0.96 for glandular tissue toxicity. Interobserver ICC was 0.78 for dermal toxicity, 0.74 for hypodermal toxicity, and 0.94 for glandular tissue toxicity. Statistical analysis found significant changes in dermal (p < 0.0001), hypodermal (p = 0.0027), and glandular tissue (p < 0.0001) assessments in the acute toxicity group. Ultrasound measurements correlated with clinical Radiation Therapy Oncology Group (RTOG) toxicity scores of patients

  15. Saltstone 4QCY14 TCLP Toxicity and UTS Results

    SciTech Connect (OSTI)

    Miller, D. H.

    2015-03-25

    A Saltstone Disposal Facility (SDF) waste form was prepared in the Savannah River National Laboratory (SRNL) from a Tank 50H sample and Z-Area premix material for the fourth quarter of calendar year 2014 (4QCY14). After a 47 day cure, a sample of the SDF waste form was collected, and shipped to a certified laboratory for Toxic Characteristic and Universal Treatment Standards (UTS) analysis. The metals analysis is performed using the Toxic Characteristic Leaching Procedure (TCLP) 1 . The 4QCY14 saltstone sample results show that the saltstone is Resource Conservation Recovery Act (RCRA) nonhazardous, but is greater than the universal treatment standard for land disposal. The Saltstone Production Facility (SPF) and SDF were in a maintenance outage during the 4QCY14. Thus no processing or disposal of saltstone, as characterized by this 4QCY14 sample, occurred.

  16. Saltstone 4QCY14 TCLP Toxicity and UTS Results

    SciTech Connect (OSTI)

    Miller, D.

    2015-03-25

    A Saltstone Disposal Facility (SDF) waste form was prepared in the Savannah River National Laboratory (SRNL) from a Tank 50H sample and Z-Area premix material for the fourth quarter of calendar year 2014 (4QCY14). After a 47 day cure, a sample of the SDF waste form was collected, and shipped to a certified laboratory for Toxic Characteristic and Universal Treatment Standards (UTS) analysis. The metals analysis is performed using the Toxic Characteristic Leaching Procedure (TCLP) . The 4QCY14 saltstone sample results show that the saltstone is Resource Conservation Recovery Act (RCRA) nonhazardous, but is greater than the universal treatment standard for land disposal. The Saltstone Production Facility (SPF) and SDF were in a maintenance outage during the 4QCY14. Thus no processing or disposal of saltstone, as characterized by this 4QCY14 sample, occurred.

  17. Saltstone 3QCY15 TCLP Toxicity and UTS Results

    SciTech Connect (OSTI)

    Miller, D.

    2015-12-09

    A Saltstone Disposal Facility (SDF) waste form was prepared in the Savannah River National Laboratory (SRNL) from a Tank 50H sample and Z-Area premix material for the third quarter of calendar year 2015 (3QCY15). After a 28 day cure, a sample of the SDF waste form was collected, and shipped to a certified laboratory for Toxic Characteristic and Universal Treatment Standards (UTS) analysis. The metals analysis is performed using the Toxic Characteristic Leaching Procedure (TCLP).1 The 3QCY15 saltstone sample results meet South Carolina Hazardous Waste Management Regulations (SCHWMR) R.61-79.261.24 and R.61-79.268.48(a) requirements for a nonhazardous waste form with respect to RCRA metals and underlying hazardous constituents (UHC).

  18. Saltone 2QCY15 TCLP toxicity and UTS results

    SciTech Connect (OSTI)

    Miller, D. H.

    2015-08-01

    A Saltstone Disposal Facility (SDF) waste form was prepared in the Savannah River National Laboratory (SRNL) from a Tank 50H sample and Z-Area premix material for the second quarter of calendar year 2015 (2QCY15). After a 28 day cure, a sample of the SDF waste form was collected, and shipped to a certified laboratory for Toxic Characteristic and Universal Treatment Standards (UTS) analysis. The metals analysis is performed using the Toxic Characteristic Leaching Procedure (TCLP)1. The 2QCY15 saltstone sample results meet South Carolina Hazardous Waste Management Regulations (SCHWMR) R.61-79.261.24 and R.61-79.268.48(a) requirements for a nonhazardous waste form with respect to RCRA metals and underlying hazardous constituents (UHC).

  19. Saltstone 2QCY15 TCLP toxicity and UTS results

    SciTech Connect (OSTI)

    Miller, D. H.

    2015-07-31

    A Saltstone Disposal Facility (SDF) waste form was prepared in the Savannah River National Laboratory (SRNL) from a Tank 50H sample and Z-Area premix material for the second quarter of calendar year 2015 (2QCY15). After a 28 day cure, a sample of the SDF waste form was collected, and shipped to a certified laboratory for Toxic Characteristic and Universal Treatment Standards (UTS) analysis. The metals analysis is performed using the Toxic Characteristic Leaching Procedure (TCLP)¹. The 2QCY15 saltstone sample results meet South Carolina Hazardous Waste Management Regulations (SCHWMR) R.61-79.261.24 and R.61-79.268.48(a) requirements for a nonhazardous waste form with respect to RCRA metals and underlying hazardous constituents (UHC).

  20. Saltstone 1QCY15 TCLP Toxicity and UTS Results

    SciTech Connect (OSTI)

    Miller, D.

    2015-07-29

    A Saltstone Disposal Facility (SDF) waste form was prepared in the Savannah River National Laboratory (SRNL) from a Tank 50H sample and Z-Area premix material for the first quarter of calendar year 2015 (1QCY15). After a 28 day cure, a sample of the SDF waste form was collected, and shipped to a certified laboratory for Toxic Characteristic and Universal Treatment Standards (UTS) analysis. The metals analysis is performed using the Toxic Characteristic Leaching Procedure (TCLP). The 1QCY15 saltstone sample results meet South Carolina Hazardous Waste Management Regulations (SCHWMR) R.61-79.261.24 and R.61-79.268.48(a) requirements for a nonhazardous waste form with respect to RCRA metals and underlying hazardous constituents (UHC).

  1. Reactive formulations for a neutralization of toxic industrial chemicals

    DOE Patents [OSTI]

    Tucker, Mark D.; Betty, Rita G.

    2006-10-24

    Decontamination formulations for neutralization of toxic industrial chemicals, and methods of making and using same. The formulations are effective for neutralizing malathion, hydrogen cyanide, sodium cyanide, butyl isocyanate, carbon disulfide, phosgene gas, capsaicin in commercial pepper spray, chlorine gas, anhydrous ammonia gas; and may be effective at neutralizing hydrogen sulfide, sulfur dioxide, formaldehyde, ethylene oxide, methyl bromide, boron trichloride, fluorine, tetraethyl pyrophosphate, phosphorous trichloride, arsine, and tungsten hexafluoride.

  2. Low toxicity method of inhibiting sickling of sickle erythrocytes

    DOE Patents [OSTI]

    Packer, Lester; Bymun, Edwin N.

    1977-01-01

    A low toxicity method of inhibiting sickling of sickle erythrocytes which comprises intermixing the erythrocytes with an effective anti-sickling amount of a water-soluble imidoester of the formula RC(=NH)OR' wherein R is an alkyl group of 1 - 8 carbon atoms, particularly 1 - 4 carbon atoms, and R' is an alkyl group of 1 - 4 carbon atoms, specifically methyl or ethyl acetimidate.

  3. Enhanced Detection of Toxic Agents - Energy Innovation Portal

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Hydropower, Wave and Tidal Hydropower, Wave and Tidal Energy Analysis Energy Analysis Advanced Materials Advanced Materials Find More Like This Return to Search Enhanced Detection of Toxic Agents Oak Ridge National Laboratory Contact ORNL About This Technology Publications: PDF Document Publication 12-G00200_1549.pdf (672 KB) Technology Marketing SummaryResearchers at ORNL and the University of Tennessee have taken the next step in the development of their AquaSentinel water quality monitoring

  4. Interaction Between Toxic Metals and Complex Biofilm/Mineral/Solution

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Interfaces highlights title by Alexis S. Templeton, Thomas P. Trainor, and Gordon E. Brown, Jr., Stanford University Sorption reactions on particle surfaces can dramatically affect the speciation, cycling and bioavailability of essential micronutrients (i.e. PO43-, Cu, Zn etc.) and toxic metals and metalloids (i.e. Pb, Hg, Se, As) in soils and aquatic environments. Considerable attention has been focused on understanding metal sorption reactions at a molecular/mechanistic level and the

  5. Comparative developmental toxicity of environmentally relevant oxygenated PAHs

    SciTech Connect (OSTI)

    Knecht, Andrea L.; Goodale, Britton C.; Truong, Lisa; Simonich, Michael T.; Swanson, Annika J.; Matzke, Melissa M.; Anderson, Kim A.; Waters, Katrina M.; Tanguay, Robert L.

    2013-09-01

    Oxygenated polycyclic aromatic hydrocarbons (OPAHs) are byproducts of combustion and photo-oxidation of parent PAHs. OPAHs are widely present in the environment and pose an unknown hazard to human health. The developing zebrafish was used to evaluate a structurally diverse set of 38 OPAHs for malformation induction, gene expression changes and mitochondrial function. Zebrafish embryos were exposed from 6 to 120 h post fertilization (hpf) to a dilution series of 38 different OPAHs and evaluated for 22 developmental endpoints. AHR activation was determined via CYP1A immunohistochemistry. Phenanthrenequinone (9,10-PHEQ), 1,9-benz-10-anthrone (BEZO), xanthone (XAN), benz(a)anthracene-7,12-dione (7,12-B[a]AQ), and 9,10-anthraquinone (9,10-ANTQ) were evaluated for transcriptional responses at 48 hpf, prior to the onset of malformations. qRT-PCR was conducted for a number of oxidative stress genes, including the glutathione transferase(gst), glutathione peroxidase(gpx), and superoxide dismutase(sod) families. Bioenergetics was assayed to measure in vivo oxidative stress and mitochondrial function in 26 hpf embryos exposed to OPAHs. Hierarchical clustering of the structure-activity outcomes indicated that the most toxic of the OPAHs contained adjacent diones on 6-carbon moieties or terminal, para-diones on multi-ring structures. 5-carbon moieties with adjacent diones were among the least toxic OPAHs while the toxicity of multi-ring structures with more centralized para-diones varied considerably. 9,10-PHEQ, BEZO, 7,12-B[a]AQ, and XAN exposures increased expression of several oxidative stress related genes and decreased oxygen consumption rate (OCR), a measurement of mitochondrial respiration. Comprehensive in vivo characterization of 38 structurally diverse OPAHs indicated differential AHR dependency and a prominent role for oxidative stress in the toxicity mechanisms. - Highlights: OPAHs are byproducts of combustion present in the environment. OPAHs pose a largely

  6. Evaluation of Chemical Warfare Agent Percutaneous Vapor Toxicity: Derivation of Toxicity Guidelines for Assessing Chemical Protective Ensembles.

    SciTech Connect (OSTI)

    Watson, A.P.

    2003-07-24

    Percutaneous vapor toxicity guidelines are provided for assessment and selection of chemical protective ensembles (CPEs) to be used by civilian and military first responders operating in a chemical warfare agent vapor environment. The agents evaluated include the G-series and VX nerve agents, the vesicant sulfur mustard (agent HD) and, to a lesser extent, the vesicant Lewisite (agent L). The focus of this evaluation is percutaneous vapor permeation of CPEs and the resulting skin absorption, as inhalation and ocular exposures are assumed to be largely eliminated through use of SCBA and full-face protective masks. Selection of appropriately protective CPE designs and materials incorporates a variety of test parameters to ensure operability, practicality, and adequacy. One aspect of adequacy assessment should be based on systems tests, which focus on effective protection of the most vulnerable body regions (e.g., the groin area), as identified in this analysis. The toxicity range of agent-specific cumulative exposures (Cts) derived in this analysis can be used as decision guidelines for CPE acceptance, in conjunction with weighting consideration towards more susceptible body regions. This toxicity range is bounded by the percutaneous vapor estimated minimal effect (EME{sub pv}) Ct (as the lower end) and the 1% population threshold effect (ECt{sub 01}) estimate. Assumptions of exposure duration used in CPE certification should consider that each agent-specific percutaneous vapor cumulative exposure Ct for a given endpoint is a constant for exposure durations between 30 min and 2 hours.

  7. Mechanisms of carbon nanotube-induced toxicity: Focus on oxidative stress

    SciTech Connect (OSTI)

    Shvedova, Anna A.; Pietroiusti, Antonio; Fadeel, Bengt; Kagan, Valerian E.

    2012-06-01

    Nanotechnologies are emerging as highly promising technologies in many sectors in the society. However, the increasing use of engineered nanomaterials also raises concerns about inadvertent exposure to these materials and the potential for adverse effects on human health and the environment. Despite several years of intensive investigations, a common paradigm for the understanding of nanoparticle-induced toxicity remains to be firmly established. Here, the so-called oxidative stress paradigm is scrutinized. Does oxidative stress represent a secondary event resulting inevitably from disruption of biochemical processes and the demise of the cell, or a specific, non-random event that plays a role in the induction of cellular damage e.g. apoptosis? The answer to this question will have important ramifications for the development of strategies for mitigation of adverse effects of nanoparticles. Recent examples of global lipidomics studies of nanoparticle-induced tissue damage are discussed along with proteomics and transcriptomics approaches to achieve a comprehensive understanding of the complex and interrelated molecular changes in cells and tissues exposed to nanoparticles. We also discuss instances of non-oxidative stress-mediated cellular damage resulting from direct physical interference of nanomaterials with cellular structures. -- Highlights: ► CNT induced non-random oxidative stress associated with apoptosis. ► Non-oxidative mechanisms for cellular toxicity of carbon nanotubes. ► Biodegradation of CNT by cells of innate immune system. ► “Omics”-based biomarkers of CNT exposures.

  8. Air toxics evaluation of ABB Combustion Engineering Low-Emission Boiler Systems

    SciTech Connect (OSTI)

    Wesnor, J.D.

    1993-10-26

    The specific goals of the program are to identify air toxic compounds that might be emmitted from the new boiler with its various Air Pollution Control device for APCD alternatives in levels of regulatory concern. For the compounds thought to be of concern, potential air toxic control methodologies will be suggested and a Test Protocol will be written to be used in the Proof of Concept and full scale tests. The following task was defined: Define Replations and Standards; Identify Air Toxic Pollutants of Interest to Interest to Utility Boilers; Assesment of Air Toxic By-Products; State of the Art Assessment of Toxic By-Product Control Technologies; and Test Protocol Definition.

  9. ROLE OF TOXICITY ASSESSMENT AND MONITORING IN MANAGING THE RECOVERY OF A WASTEWATER RECEIVING STREAM

    SciTech Connect (OSTI)

    Greeley Jr, Mark Stephen; Kszos, Lynn A; Stewart, Arthur J; Smith, John G

    2011-01-01

    We evaluate the roles of a long-term comprehensive toxicity assessment and monitoring program in management and for ecological recovery of a freshwater receiving stream impacted by industrial discharges and legacy contamination. National Pollution Discharge Elimination Permit (NPDES)-driven whole effluent toxicity (WET) tests using Ceriodaphnia and fathead minnows were conducted for more than twenty years to characterize wastewaters at the US National Nuclear Security Agency s Y-12 National Security Complex in Oak Ridge, Tennessee. Ambient toxicity tests also were conducted to assess water samples from EFPC, the stream receiving the wastewater discharges. The ambient tests were conducted as part of an extensive biological monitoring program that included routine surveys of fish, invertebrate and periphyton communities. WET testing, associated toxicant identification evaluations (TIEs), and ambient toxicity monitoring were instrumental in identifying toxicants and their sources at the Y-12 Complex, guiding modifications to wastewater treatment procedures, and assessing the success of various pollution-abatement actions. Through time, as requirements changed and water quality improved, the toxicity monitoring program became more focused. Ambient testing with Ceriodaphnia and fathead minnow larvae also was supplemented with less-standardized but more-sensitive alternative laboratory and in situ bioassays. The Y-12 Complex biological monitoring experience demonstrates the significant roles effluent and ambient toxicity testing can have in controlling and managing toxic discharges to receiving waters. It also emphasizes the value of supplementing WET and standardized ambient toxicity tests with alternative laboratory and in situ toxicity tests tailored to address specific problems.

  10. Results of acute and chronic toxicity tests conducted at SRS NPDES outfalls, July--October 1991

    SciTech Connect (OSTI)

    Specht, W.L.

    1992-01-01

    Acute (48 hour LC50) and chronic (7-day reproductive impairment) toxicity tests were conducted on Ceriodaphnia dubia in water collected from 53 NPDES outfalls. All tests were conducted at the in-stream waste concentration. only 12 of the 53 outfalls showed no evidence of toxicity. Twenty-eight of the outfalls were acutely toxic, often producing 100% mortality during the first day of exposure. Fourteen outfalls had no discharge at the time of sampling and could not be tested. Three outfalls were not tested because their toxicity has been adequately characterized in other investigations. Elevated concentrations of total residual chlorine are suspected to be responsible for the observed toxicity of many NPDES outfalls, particularly the sanitary wastewater treatment plants. Chemical data from previous studies indicate that metals may also be present in toxic concentrations at many outfalls. Toxicity identification and reduction options are discussed.

  11. Mobile Source Air Toxics Rule (released in AEO2008)

    Reports and Publications (EIA)

    2008-01-01

    On February 9, 2007, the Environmental Protection Agency (EPA) released its MSAT2 rule, which will establish controls on gasoline, passenger vehicles, and portable fuel containers. The controls are designed to reduce emissions of benzene and other hazardous air pollutants. Benzene is a known carcinogen, and the EPA estimates that mobile sources produced more than 70% of all benzene emissions in 1999. Other mobile source air toxics, including 1,3-butadiene, formaldehyde, acetaldehyde, acrolein, and naphthalene, also are thought to increase cancer rates or contribute to other serious health problems.

  12. An evaluation of the whole effluent toxicity test method

    SciTech Connect (OSTI)

    Osteen, D.V.

    1999-12-17

    Whole effluent toxicity (WET) testing has become increasingly more important to the Environmental Protection Agency (EPA) and the States in the permitting of wastewater discharges from industry and municipalities. The primary purpose of the WET test is to protect aquatic life by predicting the effect of an effluent on the receiving stream. However, there are both scientific and regulatory concerns that using WET tests to regulate industrial effluents may result in either false positives and/or false negatives. In order to realistically predict the effect of an effluent on the receiving stream, the test should be as representative as possible of the conditions in the receiving stream. Studies (Rand and Petrocelli 1985) suggested several criteria for an ideal aquatic toxicity test organism, one of which is that the organism be indigenous to, or representative of, the ecosystem receiving the effluent. The other component needed in the development of a predictive test is the use of the receiving stream water or similar synthetic water as the control and dilution water in the test method. Use of an indigenous species and receiving water in the test should help reduce the variability in the method and allow the test to predict the effect of the effluent on the receiving stream. The experience with toxicity testing at the Savannah River Site (SRS) has yielded inconclusive data because of the inconsistency and unreliability of the results. The SRS contention is that the WET method in its present form does not adequately mimic actual biological/chemical conditions of the receiving streams and is neither reasonable nor accurate. This paper discusses the rationale for such a position by SRS on toxicity testing in terms of historical permitting requirements, outfall effluent test results, standard test method evaluation, scientific review of alternate test species, and concerns over the test method expressed by other organizations. This paper presents the Savannah River Site

  13. NOx, FINE PARTICLE AND TOXIC METAL EMISSIONS FROM THE COMBUSTION OF SEWAGE SLUDGE/COAL MIXTURES: A SYSTEMATIC ASSESSMENT

    SciTech Connect (OSTI)

    Jost O.L. Wendt

    2003-01-31

    This research project focuses on pollutants from the combustion of mixtures of dried municipal sewage sludge (MSS) and coal. The objective is to determine the relationship between (1) fraction sludge in the sludge/coal mixture, and (2) combustion conditions on (a) NOx concentrations in the exhaust, (b) the size segregated fine and ultra-fine particle composition in the exhaust, and (c) the partitioning of toxic metals between vapor and condenses phases, within the process. The proposed study will be conducted in concert with an existing ongoing research on toxic metal partitioning mechanisms for very well characterized pulverized coals alone. Both high NOx and low NOx combustion conditions will be investigated (unstaged and staged combustion). Tradeoffs between CO{sub 2} control, NO{sub x} control, and inorganic fine particle and toxic metal emissions will be determined. Previous research results have demonstrated that the inhalation of coal/MSS ash particles cause an increase in lung permeability than coal ash particles alone. Elemental analysis of the coal/MSS ash particles showed that Zn was more abundant in these ash particles than the ash particles of coal ash alone.

  14. Dosimetric and Late Radiation Toxicity Comparison Between Iodine-125 Brachytherapy and Stereotactic Radiation Therapy for Juxtapapillary Choroidal Melanoma

    SciTech Connect (OSTI)

    Krema, Hatem

    2013-07-01

    Purpose: To compare the dose distributions and late radiation toxicities for {sup 125}I brachytherapy (IBT) and stereotactic radiation therapy (SRT) in the treatment of juxtapapillary choroidal melanoma. Methods: Ninety-four consecutive patients with juxtapapillary melanoma were reviewed: 30 have been treated with IBT and 64 with SRT. Iodine-125 brachytherapy cases were modeled with plaque simulator software for dosimetric analysis. The SRT dosimetric data were obtained from the Radionics XKnife RT3 software. Mean doses at predetermined intraocular points were calculated. Kaplan-Meier estimates determined the actuarial rates of late toxicities, and the logrank test compared the estimates. Results: The median follow-up was 46 months in both cohorts. The 2 cohorts were balanced with respect to pretreatment clinical and tumor characteristics. Comparisons of radiation toxicity rates between the IBT and SRT cohorts yielded actuarial rates at 50 months for cataracts of 62% and 75% (P=.1), for neovascular glaucoma 8% and 47% (P=.002), for radiation retinopathy 59% and 89% (P=.0001), and for radiation papillopathy 39% and 74% (P=.003), respectively. Dosimetric comparisons between the IBT and SRT cohorts yielded mean doses of 12.8 and 14.1 Gy (P=.56) for the lens center, 17.6 and 19.7 Gy (P=.44) for the lens posterior pole, 13.9 and 10.8 Gy (P=.30) for the ciliary body, 61.9 and 69.7 Gy (P=.03) for optic disc center, and 48.9 and 60.1 Gy (P<.0001) for retina at 5-mm distance from tumor margin, respectively. Conclusions: Late radiation-induced toxicities were greater with SRT, which is secondary to the high-dose exposure inherent to the technique as compared with IBT. When technically feasible, IBT is preferred to treat juxtapapillary choroidal melanoma.

  15. SU-E-T-206: Improving Radiotherapy Toxicity Based On Artificial Neural Network (ANN) for Head and Neck Cancer Patients

    SciTech Connect (OSTI)

    Cho, Daniel D; Wernicke, A Gabriella; Nori, Dattatreyudu; Chao, KSC; Parashar, Bhupesh; Chang, Jenghwa

    2014-06-01

    Purpose/Objective(s): The aim of this study is to build the estimator of toxicity using artificial neural network (ANN) for head and neck cancer patients Materials/Methods: An ANN can combine variables into a predictive model during training and considered all possible correlations of variables. We constructed an ANN based on the data from 73 patients with advanced H and N cancer treated with external beam radiotherapy and/or chemotherapy at our institution. For the toxicity estimator we defined input data including age, sex, site, stage, pathology, status of chemo, technique of external beam radiation therapy (EBRT), length of treatment, dose of EBRT, status of post operation, length of follow-up, the status of local recurrences and distant metastasis. These data were digitized based on the significance and fed to the ANN as input nodes. We used 20 hidden nodes (for the 13 input nodes) to take care of the correlations of input nodes. For training ANN, we divided data into three subsets such as training set, validation set and test set. Finally, we built the estimator for the toxicity from ANN output. Results: We used 13 input variables including the status of local recurrences and distant metastasis and 20 hidden nodes for correlations. 59 patients for training set, 7 patients for validation set and 7 patients for test set and fed the inputs to Matlab neural network fitting tool. We trained the data within 15% of errors of outcome. In the end we have the toxicity estimation with 74% of accuracy. Conclusion: We proved in principle that ANN can be a very useful tool for predicting the RT outcomes for high risk H and N patients. Currently we are improving the results using cross validation.

  16. Spatial and temporal variations in toxicity in a marsh receiving urban runoff

    SciTech Connect (OSTI)

    Katznelson, R.; Jewell, W.T.; Anderson, S.L.

    1993-06-01

    This project is composed of two sections. The first section describes dry weather toxicity surveys to evaluate the distribution of toxicity in the waters of San Francisco Bay and adjacent wetland habitat, and the second is a series of wet weather toxicity studies with emphasis on a marsh receiving urban runoff. The dry weather studies are reported in the appendices, while the wet weather work comprises the main report.

  17. Lung Toxicity and Mutagenicity of Emissions From Heavy-Duty Compressed

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Natural Gas (CNG)-Powered Vehicles | Department of Energy Lung Toxicity and Mutagenicity of Emissions From Heavy-Duty Compressed Natural Gas (CNG)-Powered Vehicles Lung Toxicity and Mutagenicity of Emissions From Heavy-Duty Compressed Natural Gas (CNG)-Powered Vehicles 2005 Diesel Engine Emissions Reduction (DEER) Conference Presentations and Posters 2005_deer_mauderly.pdf (324.89 KB) More Documents & Publications Relationship Between Composition and Toxicity of Engine Emission Samples

  18. Microbial stabilization and mass reduction of wastes containing radionuclides and toxic metals

    DOE Patents [OSTI]

    Francis, Arokiasamy J.; Dodge, Cleveland J.; Gillow, Jeffrey B.

    1991-01-01

    A process is provided to treat wastes containing radionuclides and toxic metals with Clostridium sp. BFGl to release a large fraction of the waste solids into solutin and convert the radionuclides and toxic metals to a more concentrated and stable form with concurrent volume and mass reduction. The radionuclides and toxic metals being in a more stable form are available for recovery, recycling and disposal.

  19. Microbial stabilization and mass reduction of wastes containing radionuclides and toxic metals

    DOE Patents [OSTI]

    Francis, A.J.; Dodge, C.J.; Gillow, J.B.

    1991-09-10

    A process is provided to treat wastes containing radionuclides and toxic metals with Clostridium sp. BFGl to release a large fraction of the waste solids into solution and convert the radionuclides and toxic metals to a more concentrated and stable form with concurrent volume and mass reduction. The radionuclides and toxic metals being in a more stable form are available for recovery, recycling and disposal. 18 figures.

  20. Pentose fermentation of normally toxic lignocellulose prehydrolysate with strain of Pichia stipitis yeast using air

    DOE Patents [OSTI]

    Keller, Jr., Fred A.; Nguyen, Quang A.

    2002-01-01

    Strains of the yeast Pichia stipitis NPw9 (ATCC PTA-3717) useful for the production of ethanol using oxygen for growth while fermenting normally toxic lignocellulosic prehydrolysates.

  1. Identification of the cause of weak acute toxicity to rainbow trout at a petroleum refinery

    SciTech Connect (OSTI)

    Arnold, W.R.; Zaleski, R.T.; Biddinger, G.R.

    1995-12-31

    The refinery in question performs flow through acute toxicity tests on its effluent four times per month using three fish species: fathead minnows (Pimephales promelas), threespine sticklebacks (Gasterosteus oculeatus) and rainbow trout (Oncorhynchus mykiss). Several months of monitoring data indicated a transient low level acute toxicity to rainbow trout. In most cases, several days were required for mortality to occur in the flow through tests and numerous attempts to reproduce toxicity in static and static renewal tests were unsuccessful. A decision was made to manipulate the effluent in an attempt to enhance the toxic effect in the static mode so that conventional methods could be used to identify the cause. these tests indicated that toxicity was pH dependent. Additional testing, using EPA`s Phase 1 Toxicity Identification Evaluation methods suggested that the cause of toxicity was probably an organic acid. Experiments were subsequently begun to identify the specific cause and source of toxicity. This paper reviews the problems confronted during the various phases of the study and the decisions that were made that eventually led to an understanding of the basis of toxicity.

  2. Summary of EPA Final Rules for Air Toxic Standards for Industrial...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    This summary of EPA Final Rules for Air Toxic Standards for Industrial, Commercial, and ... December 2012 Boiler Maximum Achievable Control Technology (MACT) Technical Assistance - ...

  3. On-Line Microbial Whole Effluent Toxicity Monitoring for Industrial Wastewater

    SciTech Connect (OSTI)

    Mathews, S; Hoppes, W; Mascetti, M; Campbell, C G

    2002-09-17

    In this study a respirometer is tested for its ability to act as an early upset warning device and whole effluent toxicity monitor for industrial discharge. Industrial discharge water quality is commonly evaluated by comparing measured chemical concentrations to target values or regulatory limits established by governmental agencies. Unless the regulatory values are based upon empirical data, the actual effect of the discharge on aquatic systems is unknown. At the same time assessing the environmental toxicology of wastewater discharges is complicated by synergistic relationships among chemical constituents producing greater total toxicity. For example, metals may be more toxic in waters with low total hardness or more soluble at lower pH. An alternative approach that we are investigating is whole effluent toxicity testing. This study investigates the measurement of whole effluent toxicity through an on-line respirometer that measures toxicity to microorganisms comprising activated sludge. In this approach the oxygen uptake rate is monitored and used as an indicator of microbial activity or health. This study investigates the use of an online whole effluent toxicity testing system to provide early upset warning and the consistency of measured response to low pH. Repeated exposure of the microorganisms to low pH results in reduced sensitivity of the microbial population. We investigate whether this reduction in sensitivity results from physiological acclimation or changes in species composition. We identify promising applications, where, with proper calibration, respirometry based toxicity monitoring appear to be well suited for relative comparisons of whole effluent toxicity.

  4. Toxic substances form coal combustion--a co prehemsice assessment

    SciTech Connect (OSTI)

    Huggins, F.; Huffman, G.P.; Shah, N.

    1997-04-01

    The Clean Coal Act Amendments of 1990 identify a number of hazardous air pollutants as candidates for regulation. Should regulations be imposed on emission of these pollutants from coal-fired power plants, a sound understanding of the fundamental principles controlling their formation and partition will be needed. A new Toxics Partitioning Engineering Model (ToPEM) has been developed by a broad consortium to be useful to regulators and utility planners. During the last quarter coal analysis was completed on the final program coal, from the Wyodak Seam of the Powder River Basin, Combustion testing continued, including data collected on the self-sustained combustor. Efforts were directed to identify the governing mechanisms for trace element vaporization from the program coals. Mercury speciation and measurements were continued. Review of the existing trace element and organics emission literature was completed. And, model development was begun.

  5. Microcurrent therapeutic technique for treatment of radiation toxicity

    DOE Patents [OSTI]

    Lennox, Arlene; Funder, Sandra

    2000-01-01

    The present technique provides a method of remediating the toxicities associated with radiation therapy. A conductive gel is applied to the affected bodily area. A sinusoidally pulsed biphasic DC current is then applied to the affected bodily area using at least one electrode. The electrode is manipulated using active tactile manipulation by for a predetermined time and the frequency of the sinusoidally pulsed biphasic DC current is decreased during the course of the treatment. The method also includes applying a spiked pulsed biphasic DC current to the affected bodily area using at least one electrode. This electrode is also manipulated using active tactile manipulation by for a predetermined time and the frequency of the spiked pulsed biphasic DC current is also decreased during the course of the treatment.

  6. TOXIC SUBSTANCES FROM COAL COMBUSTION: A COMPREHENSIVE ASSESSMENT

    SciTech Connect (OSTI)

    C.L. Senior; T. Panagiotou; J.O.L. Wendt; W. Seames; F.E. Huggins; G.P Huffman; N. Yap; M.R. Ames; I.Olmez; T. Zeng; A.F. Sarofim; A. Kolker; R. Finkelman; J.J. Helble

    1998-07-16

    The Clean Air Act Amendments of 1990 identify a number of hazardous air pollutants (HAPs) as candidates for regulation. Should regulations be imposed on HAP emissions from coal-fired power plants, a sound understanding of the fundamental principles controlling the formation and partitioning of toxic species during coal combustion will be needed. With support from the Federal Energy Technology Center (FETC), the Electric Power Research Institute, and VTT (Finland), Physical Sciences Inc. (PSI) has teamed with researchers from USGS, the Massachusetts Institute of Technology (MIT), the University of Arizona (UA), the University of Kentucky (UK), the University of Connecticut (UC), the University of Utah (W) and the University of North Dakota Energy and Environmental Research Center (EERC) to develop a broadly applicable emissions model useful to regulators and utility planners. The new Toxics Partitioning Engineering Model (ToPEM) will be applicable to all combustion conditions including new fuels and coal blends, low-NO{sub x} combustion systems, and new power generation plants. Development of ToPEM will be based on PSI's existing Engineering Model for Ash Formation (EMAF). This report covers the reporting period from the submission of the draft Phase 1 Final Report through the end of June, 1998. During this period two of the three Phase 2 coals were procured and pulverized samples were distributed to team members. Analysis of Phase 1 X-Ray Absorption Fine Structure (XAFS) data, particularly of mercury in sorbent samples, continued. An improved method for identifying mercury compounds on sorbents was developed, leading to a clearer understanding of forms of mercury in char and sorbents exposed to flue gas. Additional analysis of Phase 1 large scale combustion data was performed to investigate mechanistic information related to the fate of the radionuclides Cs, Th, and Co. Modeling work for this period was focused on building and testing a sub-model for vaporization

  7. Flavanone silibinin treatment attenuates nitrogen mustard-induced toxic effects in mouse skin

    SciTech Connect (OSTI)

    Jain, Anil K.; Tewari-Singh, Neera; Inturi, Swetha; Kumar, Dileep; Orlicky, David J.; Agarwal, Chapla; White, Carl W.; Agarwal, Rajesh

    2015-05-15

    Currently, there is no effective antidote to prevent skin injuries by sulfur mustard (SM) and nitrogen mustard (NM), which are vesicating agents with potential relevance to chemical warfare, terrorist attacks, or industrial/laboratory accidents. Our earlier report has demonstrated the therapeutic efficacy of silibinin, a natural flavanone, in reversing monofunctional alkylating SM analog 2-chloroethyl ethyl sulfide-induced toxic effects in mouse skin. To translate this effect to a bifunctional alkylating vesicant, herein, efficacy studies were carried out with NM. Topical application of silibinin (1 or 2 mg) 30 min after NM exposure on the dorsal skin of male SKH-1 hairless mice significantly decreased NM-induced toxic lesions at 24, 72 or 120 h post-exposure. Specifically, silibinin treatment resulted in dose-dependent reduction of NM-induced increase in epidermal thickness, dead and denuded epidermis, parakeratosis and microvesication. Higher silibinin dose also caused a 79% and 51%reversal in NM-induced increases in myeloperoxidase activity and COX-2 levels, respectively. Furthermore, silibinin completely prevented NM-induced H2A.X phosphorylation, indicating reversal of DNA damage which could be an oxidative DNA damage as evidenced by high levels of 8-oxodG in NM-exposed mouse skin that was significantly reversed by silibinin. Together, these findings suggest that attenuation of NM-induced skin injury by silibinin is due to its effects on the pathways associated with DNA damage, inflammation, vesication and oxidative stress. In conclusion, results presented here support the optimization of silibinin as an effective treatment of skin injury by vesicants. - Highlights: • Silibinin treatment attenuated nitrogen mustard (NM)-induced skin injury. • Silibinin affects pathways associated with DNA damage, inflammation and vesication. • The efficacy of silibinin could also be associated with oxidative stress. • These results support testing and optimization of

  8. Air toxic emissions from the combustion of coal: Identifying and quantifying hazardous air pollutants from US coals

    SciTech Connect (OSTI)

    Szpunar, C.B.

    1992-09-01

    This report addresses the key air toxic emissions likely to emanate from continued and expanded use of domestic coal. It identifies and quantifies those trace elements specified in the US 1990 Clean Air Act Amendments, by tabulating selected characterization data on various source coals by region, state, and rank. On the basis of measurements by various researchers, this report also identifies those organic compounds likely to be derived from the coal combustion process (although their formation is highly dependent on specific boiler configurations and operating conditions).

  9. In situ toxicity evaluations of turbidity and photoinduction of polycyclic aromatic hydrocarbons

    SciTech Connect (OSTI)

    Ireland, D.S.; Burton, G.A. Jr; Hess, G.G.

    1996-04-01

    Polycyclic aromatic hydrocarbons (PAHs) are prevalent pollutants in the aquatic environment that can cause a wide range of toxic effects. Earlier studies have shown that toxicity of PAHs can be enhanced by ultraviolet (UV) radiation. In situ and laboratory exposures with Ceriodaphnia dubia were used to evaluate photoinduced toxicity of PAHs in wet-weather runoff and in turbid conditions. Exposure to UV increased the toxicity of PAH-contaminated sediment to C. dubia. Toxicity was removed when UV wavelengths did not penetrate the water column to the exposed organisms. A significant correlation was observed between in situ C. dubia survival and turbidity when organisms were exposed to sunlight. Stormwater runoff samples exhibited an increase in chronic toxicity (reproduction) to C. dubia when exposed to UV wavelengths as compared to C. dubia not exposed to UV wavelengths. Toxicity was reduced significantly in the presence of UV radiation when the organic fraction of stormwater runoff was removed. The PAHs are bound to the sediment and resuspended into the water column once the sediment is disturbed (e.g., during a storm). The in situ and laboratory results showed that photoinduced toxicity occurred frequently during low flow conditions and wet weather runoff and was reduced in turbid conditions.

  10. Toxic substances from coal combustion -- A comprehensive assessment

    SciTech Connect (OSTI)

    Senior, C.L.; Panagiotou, T.; Huggins, F.E.; Huffman, G.P.; Yap, N.; Wendt, J.O.L.; Seames, W.; Ames, M.R.; Sarofim, A.F.; Lighty, J.; Kolker, A.; Finkelman, R.; Palmer, C.A.; Mroczkowsky, S.J.; Helble, J.J.; Mamani-Paco, R.

    1999-07-30

    The Clean Air Act Amendments of 1990 identify a number of hazardous air pollutants (HAPs) as candidates for regulation. Should regulations be imposed on HAP emissions from coal-fired power plants, a sound understanding of the fundamental principles controlling the formation and partitioning of toxic species during coal combustion will be needed. With support from the Federal Energy Technology Center (FETC), the Electric Power Research Institute, and VTT (Finland), Physical Sciences Inc. (PSI) has teamed with researchers from USGS, MIT, the University of Arizona (UA), the University of Kentucky (UK), the University of Connecticut (UC), the University of Utah (UU) and the University of North Dakota Energy and Environmental Research Center (EERC) to develop a broadly applicable emissions model useful to regulators and utility planners. The new Toxics Partitioning Engineering Model (ToPEM) will be applicable to all combustion conditions including new fuels and coal blends, low-NOx combustion systems, and new power generation plants. Development of ToPEM will be based on PSI's existing Engineering Model for Ash Formation (EMAF). This report covers the period from 1 April 1999 to 30 June 1999. During this quarter low temperature ashing and elemental analysis of the three Phase II coals were completed. Results from MIT and USGS are comparable. Plans were made for measurements of loss of trace elements during devolatilization and for single particle combustion studies at the University of Utah. The iodated charcoal trap was tested on coal combustion flue gas and was shown to collect both Hg and Se in from the vapor phase with 100% efficiency. Data from the University of Arizona self-sustained combustor were analyzed from the combustion of three coals: Ohio, Wyodak and Illinois No. 6. Ash size distributions and enrichment factors for selected trace elements were calculated. The correlation between the concentration of the more volatile trace elements in the ash and the

  11. A novel nanoparticle-based disposable electrochemical immunosensor for diagnosis of exposure to toxic organophosphorus agents

    SciTech Connect (OSTI)

    Lu, Donglai; Wang, Jun; Wang, Limin; Du, Dan; Timchalk, Charles; Barry, Richard C.; Lin, Yuehe

    2011-11-15

    We present a novel disposable electrochemical immunosensor for highly selective and sensitive detection of organophosphorylated butyrylcholinesterase (OP-BChE), a specific biomarker for exposure to toxic organophosphorus agents. In our new approach, the zirconia nanoparticles (ZrO-2) were employed to selectively capture the OP moiety of OP-BChE adducts, and followed by quantum dot (QD)-tagged anti-BChE antibodies for amplified quantification. The captured CdSe-QD tags can be sensitively detected by stripping voltammetry using in situ bismuth-plating method. The OP agent, diisopropylfluorophosphate (DFP), was selected to prepare OP-BChE adducts in various matrices. The formation of OP-BChE adducts in plasma sample was confirmed using mass spectroscopy. The developed electrochemical immunosensor demonstrates a highly linear voltammetric response over the range of 0.1 to 30 nM OP-BChE. Moreover, the immunosensor has been successfully applied for the detection of OP-BChE adducts in the plasma samples. This novel nanoparticle-based electrochemical immunosensor thus provides an alternative way for designing simple, fast, sensitive, and cost-effective sensing platform for on-site screening/evaluating exposure to a variety of OP agents.

  12. Gene expression patterns in Rainbow Trout, Oncorhynchus mykiss, exposed to a suite of model toxicants

    SciTech Connect (OSTI)

    Hook, Sharon E.; Skillman, Ann D.; Small, Jonathan A.; Schultz, Irv R.

    2006-05-25

    The increased availability and use of DNA microarrays has allowed the characterization of gene expression patterns associated with different toxicants. An important question is whether toxicant induced changes in gene expression in fish are sufficiently diverse to allow for identification of specific modes of action and/or specific contaminants. In theory, each class of toxicant may generate a gene expression profile unique to its mode of toxic action. We exposed isogenic (cloned) rainbow trout Oncorhyncus mykiss, to sublethal levels of a series of model toxicants with varying modes of action, including ethynylestradiol (xeno-estrogen), trenbolone (anabolic steroid; model androgen), 2,2,4,4´tetrabromodiphenyl ether (BDE-47, thyroid active), diquat (oxidant stressor), chromium VI, and benzo[a]pyrene (BaP) for a period of 1-3 weeks. Following exposure, fish were euthanized, livers harvested and RNA extracted. Fluorescently labeled cDNA were generated and hybridized against a commercially available Atlantic Salmon / Trout array (GRASP project, University of Victoria) spotted with 16,000 cDNA’s. The slides were scanned to measure abundance of a given transcript in each sample relative to controls. Data were analyzed via Genespring (Silicon Genetics) to identify a list of up and down regulated genes, as well as to determine gene clustering patterns that can be used as “expression signatures”. Our analysis indicates each toxicant generated specific gene expression profiles. Most genes exhibiting altered expression responded to only one of the toxicants. Relatively few genes are co-expressed in multiple treatments. For example, BaP and Diquat, both of which exert toxicity via oxidative stress, up-regulated 28 of the same genes, of over 100 genes altered by ether treatment. Other genes associated with steroidogenesis, p450 and estrogen responsive genes appear to be useful for selectively identifying toxicant mode of in fish, suggesting a link between gene expression

  13. Spot Scanning Proton Therapy for Malignancies of the Base of Skull: Treatment Planning, Acute Toxicities, and Preliminary Clinical Outcomes

    SciTech Connect (OSTI)

    Grosshans, David R.; Zhu, X. Ronald; Melancon, Adam; Allen, Pamela K.; Poenisch, Falk; Palmer, Matthew; McAleer, Mary Frances; McGovern, Susan L.; Gillin, Michael; DeMonte, Franco; Chang, Eric L.; Brown, Paul D.; Mahajan, Anita

    2014-11-01

    Purpose: To describe treatment planning techniques and early clinical outcomes in patients treated with spot scanning proton therapy for chordoma or chondrosarcoma of the skull base. Methods and Materials: From June 2010 through August 2011, 15 patients were treated with spot scanning proton therapy for chordoma (n=10) or chondrosarcoma (n=5) at a single institution. Toxicity was prospectively evaluated and scored weekly and at all follow-up visits according to Common Terminology Criteria for Adverse Events, version 3.0. Treatment planning techniques and dosimetric data were recorded and compared with those of passive scattering plans created with clinically applicable dose constraints. Results: Ten patients were treated with single-field-optimized scanning beam plans and 5 with multifield-optimized intensity modulated proton therapy. All but 2 patients received a simultaneous integrated boost as well. The mean prescribed radiation doses were 69.8 Gy (relative biological effectiveness [RBE]; range, 68-70 Gy [RBE]) for chordoma and 68.4 Gy (RBE) (range, 66-70) for chondrosarcoma. In comparison with passive scattering plans, spot scanning plans demonstrated improved high-dose conformality and sparing of temporal lobes and brainstem. Clinically, the most common acute toxicities included fatigue (grade 2 for 2 patients, grade 1 for 8 patients) and nausea (grade 2 for 2 patients, grade 1 for 6 patients). No toxicities of grades 3 to 5 were recorded. At a median follow-up time of 27 months (range, 13-42 months), 1 patient had experienced local recurrence and a second developed distant metastatic disease. Two patients had magnetic resonance imaging-documented temporal lobe changes, and a third patient developed facial numbness. No other subacute or late effects were recorded. Conclusions: In comparison to passive scattering, treatment plans for spot scanning proton therapy displayed improved high-dose conformality. Clinically, the treatment was well tolerated, and

  14. Results of Toxicity Studies Conducted on Outfall X-08 and Its Contributing Waste Streams, November 1999 - June 2000

    SciTech Connect (OSTI)

    Specht, W.L.

    2000-06-28

    This interim report summarizes the results of toxicity tests, Toxicity Identification Evaluations, and chemical analyses that have been conducted on SRS's NPDES Outfall X-08 and its contributing waste streams between November 1999 and June 2000.

  15. NOx, FINE PARTICLE AND TOXIC METAL EMISSIONS FROM THE COMBUSTION OF SEWAGE SLUDGE/COAL MIXTURES: A SYSTEMATIC ASSESSMENT

    SciTech Connect (OSTI)

    Jost O.L. Wendt

    2002-02-05

    This research project focuses on pollutants from the combustion of mixtures of dried municipal sewage sludge (MSS) and coal. The objective is to determine the relationship between (1) fraction sludge in the sludge/coal mixture, and (2) combustion conditions on (a) NO{sub x} concentrations in the exhaust, (b) the size segregated fine and ultra-fine particle composition in the exhaust, and (c) the partitioning of toxic metals between vapor and condenses phases, within the process. To this end work is progress using an existing 17kW downflow laboratory combustor, available with coal and sludge feed capabilities. The proposed study will be conducted in concert with an existing ongoing research on toxic metal partitioning mechanisms for very well characterized pulverized coals alone. Both high NO{sub x} and low NO{sub x} combustion conditions will be investigated (unstaged and staged combustion). The proposed work uses existing analytical and experimental facilities and draws on 20 years of research on NO{sub x} and fine particles that has been funded by DOE in this laboratory. Four barrels of dried sewage sludge are currently in the laboratory. Insofar as possible pertinent mechanisms will be elucidated. Tradeoffs between CO{sub 2} control, NO{sub x} control, and inorganic fine particle and toxic metal emissions will be determined. Progress in the Sixth Quarter (January 1, 2002 through March 31, 2002) was slow because of slagging problems in the combustor. These required the combustor to be rebuilt, a job that is not yet complete. A paper describing our results heretofore has been accepted by the Journal Environmental Science and Technology.

  16. Mechanism of imidazolium ionic liquids toxicity in Saccharomyces cerevisiae and rational engineering of a tolerant, xylose-fermenting strain

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Dickinson, Quinn; Bottoms, Scott; Hinchman, Li; McIlwain, Sean; Li, Sheena; Myers, Chad L.; Boone, Charles; Coon, Joshua J.; Hebert, Alexander; Sato, Trey K.; et al

    2016-01-20

    In this study, imidazolium ionic liquids (IILs) underpin promising technologies that generate fermentable sugars from lignocellulose for future biorefineries. However, residual IILs are toxic to fermentative microbes such as Saccharomyces cerevisiae, making IIL-tolerance a key property for strain engineering. To enable rational engineering, we used chemical genomic profiling to understand the effects of IILs on S. cerevisiae. As a result, we found that IILs likely target mitochondria as their chemical genomic profiles closely resembled that of the mitochondrial membrane disrupting agent valinomycin. Further, several deletions of genes encoding mitochondrial proteins exhibited increased sensitivity to IIL. High-throughput chemical proteomics confirmed effectsmore » of IILs on mitochondrial protein levels. IILs induced abnormal mitochondrial morphology, as well as altered polarization of mitochondrial membrane potential similar to valinomycin. Deletion of the putative serine/threonine kinase PTK2 thought to activate the plasma-membrane proton efflux pump Pma1p conferred a significant IIL-fitness advantage. Conversely, overexpression of PMA1 conferred sensitivity to IILs, suggesting that hydrogen ion efflux may be coupled to influx of the toxic imidazolium cation. PTK2 deletion conferred resistance to multiple IILs, including [EMIM]Cl, [BMIM]Cl, and [EMIM]Ac. An engineered, xylose-converting ptk2Δ S. cerevisiae (Y133-IIL) strain consumed glucose and xylose faster and produced more ethanol in the presence of 1 % [BMIM]Cl than the wild-type PTK2 strain. We propose a model of IIL toxicity and resistance. In conclusion, this work demonstrates the utility of chemical genomics-guided biodesign for development of superior microbial biocatalysts for the ever-changing landscape of fermentation inhibitors.« less

  17. Process safety management for highly hazardous chemicals

    SciTech Connect (OSTI)

    1996-02-01

    Purpose of this document is to assist US DOE contractors who work with threshold quantities of highly hazardous chemicals (HHCs), flammable liquids or gases, or explosives in successfully implementing the requirements of OSHA Rule for Process Safety Management of Highly Hazardous Chemicals (29 CFR 1910.119). Purpose of this rule is to prevent releases of HHCs that have the potential to cause catastrophic fires, explosions, or toxic exposures.

  18. Acute toxicity of selected metals and phenols on RTG-2 and CHSE-214 fish cell lines

    SciTech Connect (OSTI)

    Castano, A. |; Vega, M.M.; Tarazona, J.V.

    1995-08-01

    In vitro toxicity tests with fish cell lines appear as an alternative to single species bioassays and have been used successfully in different applications, both for single chemicals and for environmental samples, including Toxicity Identification Evaluation procedures. Different fish cell lines, such as BF-2, RTG-2, FHM and R1 have been employed in these toxicological studies. The aim of the present study was to compare the sensitivity of two salmonid fish cell lines, RTG-2 and CHSE-214, in evaluating toxicity of seven compounds (three metals and four phenolic chemicals), by measuring three endpoints: cellular mass, cell viability and intracellular ATP content of the cells. 22 refs., 3 figs., 1 tab.

  19. Toxic substances from coal combustion -- A comprehensive assessment

    SciTech Connect (OSTI)

    C.L. Senior; T. Panagiotou; F.E. Huggins; G.P. Huffman; N. Yap; J.O.L. Wendt; W. Seames; M.R. Ames; A.F Sarofim; J. Lighty; A. Kolker; R. Finkelman; C.A. Palmer; S.J. Mroczkowsky; J.J. Helble; R. Mamani-Paco

    1999-11-01

    The Clean Air Act Amendments of 1990 identify a number of hazardous air pollutants (HAPs) as candidates for regulation. Should regulations be imposed on HAP emissions from coal-fired power plants, a sound understanding of the fundamental principles controlling the formation and partitioning of toxic species during coal combustion will be needed. With support from the Federal Energy Technology Center (FETC), the Electric Power Research Institute, and VTT (Finland), Physical Sciences Inc. (PSI) has teamed with researchers from USGS, MIT, the University of Arizona (UA), the University of Kentucky (UK), the University of Connecticut (UC), the University of Utah (UU) and the University of North Dakota Energy and Environmental Research Center (EERC) to develop a broadly applicable emissions model useful to regulators and utility planners. The new Toxics Partitioning Engineering Model (ToPEM) will be applicable to all combustion conditions including new fuels and coal blends, low-NOx combustion systems, and new power generation plants. Development of ToPEM will be based on PSI's existing Engineering Model for Ash Formation (EMAF). This report covers the reporting period from 1 July 1999 to 30 September 1999. During this period the MIT INAA procedures were revised to improve the quality of the analytical results. Two steps have been taken to reduce the analytical errors. A new nitric acid leaching procedure, modified from ASTM procedure D2492, section 7.3.1 for determination of pyritic sulfur, was developed by USGS and validated. To date, analytical results have been returned for all but the last complete round of the four-step leaching procedure. USGS analysts in Denver have halted development of the cold vapor atomic fluorescence technique for mercury analysis procedure in favor of a new direct analyzer for Hg that the USGS is in the process of acquiring. Since early June, emphasis at USGS has been placed on microanalysis of clay minerals in project coals in preparation

  20. Analysis of the toxicity in Rocky Flats Plant surface water through a correlation between the whole effluent toxicity test and the Microtox assay

    SciTech Connect (OSTI)

    Ford, S.M.; Wolaver, H.A.; Figueroa, L.A.

    1992-07-01

    Results were correlated from the Microtox assay and the whole effluent acute toxicity test for effluents from the (1) wastewater treatment plant (WWTP) and (2) terminal ponds located at the Rocky Flats Plant. Literature reviews indicate that Photobacterium phosphoreum (Microtox assay) may be used as screening test for the reaction of Ceriodaphnia dubia and Pimephales promelas to toxins present in effluents. This study indicates that the Microtox is less sensitive to toxins present in the WWTP effluent than other test organisms (Ceriodaphnia dubia and Pimephales promelas). Toxicity appears to be from unionized ammonia. Ten months of data reveal that the surface water effluents which leave Rocky Flats boundaries are non-toxic when judged by all three test organisms.

  1. Analysis of the toxicity in Rocky Flats Plant surface water through a correlation between the whole effluent toxicity test and the Microtox assay

    SciTech Connect (OSTI)

    Ford, S.M.; Wolaver, H.A. ); Figueroa, L.A. )

    1992-01-01

    Results were correlated from the Microtox assay and the whole effluent acute toxicity test for effluents from the (1) wastewater treatment plant (WWTP) and (2) terminal ponds located at the Rocky Flats Plant. Literature reviews indicate that Photobacterium phosphoreum (Microtox assay) may be used as screening test for the reaction of Ceriodaphnia dubia and Pimephales promelas to toxins present in effluents. This study indicates that the Microtox is less sensitive to toxins present in the WWTP effluent than other test organisms (Ceriodaphnia dubia and Pimephales promelas). Toxicity appears to be from unionized ammonia. Ten months of data reveal that the surface water effluents which leave Rocky Flats boundaries are non-toxic when judged by all three test organisms.

  2. Tumor histology and location predict deep nuclei toxicity: Implications for late effects from focal brain irradiation

    SciTech Connect (OSTI)

    Plaga, Alexis; Shields, Lisa B.E.; Sun, David A.; Vitaz, Todd W.; Spalding, Aaron C.

    2012-10-01

    Normal tissue toxicity resulting from both disease and treatment is an adverse side effect in the management of patients with central nervous system malignancies. We tested the hypothesis that despite these improvements, certain tumors place patients at risk for neurocognitive, neuroendocrine, and neurosensory late effects. Defining patient groups at risk for these effects could allow for development of preventive strategies. Fifty patients with primary brain tumors underwent radiation planning with magnetic resonance imaging scan and computed tomography datasets. Organs at risk (OAR) responsible for neurocognitive, neuroendocrine, and neurosensory function were defined. Inverse-planned intensity-modulated radiation therapy was optimized with priority given to target coverage while penalties were assigned to exceeding normal tissue tolerances. Tumor laterality, location, and histology were compared with OAR doses, and analysis of variance was performed to determine the significance of any observed correlation. The ipsilateral hippocampus exceeded dose limits in frontal (74%), temporal (94%), and parietal (100%) lobe tumor locations. The contralateral hippocampus was at risk in the following tumor locations: frontal (53%), temporal (83%), or parietal (50%) lobe. Patients with high-grade glioma were at risk for ipsilateral (88%) and contralateral (73%) hippocampal damage (P <0.05 compared with other histologies). The pituitary gland and hypothalamus exceeded dose tolerances in patients with pituitary tumors (both 100%) and high-grade gliomas (50% and 75%, P <0.05 compared with other histologies), respectively. Despite application of modern radiation therapy, certain tumor locations and histologies continue to place patients at risk for morbidity. Patients with high-grade gliomas or tumors located in the frontal, temporal, or parietal lobes are at risk for neurocognitive decline, likely because of larger target volumes and higher radiation doses. Data from this study

  3. Application of powder metallurgy techniques for the development of non-toxic ammunition. Final CRADA report

    SciTech Connect (OSTI)

    Lowden, R.; Kelly, R.

    1997-05-30

    The purpose of the Cooperative Research and Development Agreement (CRADA) between Martin Marietta Energy Systems, Inc., and Delta Frangible Ammunition (DFA), was to identify and evaluate composite materials for the development of small arms ammunition. Currently available small arms ammunition utilizes lead as the major component of the projectile. The introduction of lead into the environment by these projectiles when they are expended is a rapidly increasing environmental problem. At certain levels, lead is a toxic metal to the environment and a continual health and safety concern for firearm users as well as those who must conduct lead recovery operations from the environment. DFA is a leading supplier of high-density mixtures, which will be used to replace lead-based ammunition in specific applications. Current non-lead ammunition has several limitations that prevent it from replacing lead-based ammunition in many applications (such as applications that require ballistics, weapon recoil, and weapon function identical to that of lead-based ammunition). The purpose of the CRADA was to perform the research and development to identify cost-effective materials to be used in small arms ammunition that eventually will be used in commercially viable, environmentally conscious, non-lead, frangible and/or non-frangible, ammunition.

  4. Hematologic Toxicity in RTOG 0418: A Phase 2 Study of Postoperative IMRT for Gynecologic Cancer

    SciTech Connect (OSTI)

    Klopp, Ann H.; Moughan, Jennifer; Portelance, Lorraine; Miller, Brigitte E.; Salehpour, Mohammad R.; Hildebrandt, Evangeline; Nuanjing, Jenny; D'Souza, David; Souhami, Luis; Small, William; Gaur, Rakesh; Jhingran, Anuja

    2013-05-01

    associated with low rates of HT and high rates of weekly cisplatin use. The volume of bone marrow receiving 40 Gy and the median dose to bone marrow correlated with higher rates of grade ?2 toxicity among patients receiving weekly cisplatin (cervical cancer patients). Evaluation and limitation of the volume of bone marrow treated with pelvic IMRT is warranted in patients receiving concurrent chemotherapy.

  5. WAC 173-460 - Controls for New Sources of Toxic Air Pollutants...

    Open Energy Info (EERE)

    73-460 - Controls for New Sources of Toxic Air Pollutants Jump to: navigation, search OpenEI Reference LibraryAdd to library Legal Document- RegulationRegulation: WAC 173-460 -...

  6. U.S./Mexico Border environmental study toxics release inventory data, 1988--1992

    SciTech Connect (OSTI)

    O`Brien, R.F.; LoPresti, C.A.

    1996-02-01

    This is a report on industrial toxic chemical releases and transfers based on information reported to the Toxics Release Inventory (TRI), a database maintained by the USEPA. This document discusses patterns of toxic chemical releases to the atmosphere, to water, to the land, and to underground injection; and transfers of toxic chemicals to Publicly Owned Treatment Works (POTW), and for disposal, treatment and other off-site transfers during the TRI reporting years 1988--1992. Geographic coverage is limited to the US side of the ``Border Area``, the geographic area situated within 100 km of the US/Mexico international boundary. A primary purpose of this study is to provide background information that can be used in the future development of potential ``indicator variables`` for tracking environmental and public health status in the Border Area in conjunction with the implementation of the North American Free Trade Agreement (NAFTA).

  7. New Tool for Studying Toxic Metals in the Environment | U.S....

    Office of Science (SC) Website

    Organic thiols are a class of reduced sulfur compounds that occur in soil, fresh, and marine water environments. Thiols are known to react and form complexes with several toxic ...

  8. Chronic toxicity of 14 phthalate esters to Daphnia magna and rainbow trout (Oncorhynchus mykiss)

    SciTech Connect (OSTI)

    Rhodes, J.E.; Adams, W.J.; Biddinger, G.R.; Robillard, K.A.; Gorsuch, J.W.

    1995-11-01

    Chronic toxicity studies were performed with commercial phthalate esters and Daphnia magna (14 phthalates) and rainbow trout (Oncorhynchus mykiss) (six phthalates). For the lower-molecular-weight phthalate esters--dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP), and butylbenzyl phthalate (BBP)--the results of the studies indicated a general trend in which toxicity for both species increased as water solubility decreased. The geometric mean maximum acceptable toxicant concentration(GM-MATC) for D. magna ranged from 0.63 to 34.8 mg/L. For the higher-molecular-weight phthalate esters--dihexyl phthalate (DHP), butyl 2-ethylhexyl phthalate (BOP), di-(n-hexyl, n-octyl, n-decyl) phthalate (610P), di-(2-ethylhexyl) phthalate (DEHP), diisooctyl phthalate (DIOP), diisononyl phthalate (DINP), di-(heptyl, nonyl, undecyl) phthalate (711P), diisodecyl phthalate (DIDP), diundecyl phthalate (DUP), and ditridecyl phthalate (DTDP)--the GM-MATC values ranged from 0.042 to 0.15 mg/L. Survival was equally sensitive and sometimes more sensitive than reproduction. The observed toxicity to daphnids with most of the higher-molecular-weight phthalate esters appeared to be due to surface entrapment or a mode of toxicity that is not due to exposure to dissolved aqueous-phase chemical. Early life-stage toxicity studies with rainbow trout indicated that survival (DMP) and growth (DBP) were affected at 24 and 0.19 mg/L, respectively. This pattern of observed toxicity with the lower-molecular-weight phthalate esters and not the higher-molecular-weight phthalate esters is consistent with previously reported acute toxicity studies for several aquatic species.

  9. A Review of Toxicity and Use and Handling Considerations for Guanidine, Guanidine Hydrochloride, and Urea.

    SciTech Connect (OSTI)

    Ertell, Katherine GB

    2006-03-27

    This is a technical report prepared for Oregon Sustainable Energy, LLC, under Agreement 06-19 with PNNL's Office of Small Business Programs. The request was to perform a review of the toxicity and safe handling of guanidine. The request was later amended to add urea. This report summarizes the toxicity data available in the scientific literature and provides an interpretation of the results and recommendations for handling these compounds.

  10. Species-specific toxicity of troglitazone on rats and human by gel entrapped hepatocytes

    SciTech Connect (OSTI)

    Shen, Chong; Meng, Qin; Zhang, Guoliang

    2012-01-01

    Troglitazone, despite passing preclinical trials on animals, was shortly withdrawn from market due to its severe hepatotoxicity in clinic. As rat hepatocyte monolayer consistently showed sensitive troglitazone toxicity as human hepatocyte monolayer in contrast to the species-specific toxicity in vivo, this paper utilized both hepatocytes in three-dimensional culture of gel entrapment to reflect the species difference on hepatotoxicity. Rat hepatocytes in gel entrapment did not show obvious cellular damage even under a long-term exposure for 21 days while gel entrapped human hepatocytes significantly displayed oxidative stress, steatosis, mitochondrial damage and cell death at a short exposure for 4 days. As a result, the detected species-specific toxicity of troglitazone between gel entrapped rat and human hepatocytes consisted well with the situation in vivo but was in a sharp contrast to the performance of two hepatocytes by monolayer culture. Such contradictory toxicity of rat hepatocytes between monolayer and gel entrapment culture could be explained by the fact that troglitazone was cleared more rapidly in gel entrapment than in monolayer culture. Similarly, the differential clearance of troglitazone in rat and human might also explain its species-specific toxicity. Therefore, gel entrapment of hepatocytes might serve as a platform for evaluation of drug toxicity at early stage of drug development by reducing costs, increasing the likelihood of clinical success and limiting human exposure to unsafe drugs. -- Highlights: ► Species-specific toxicity of troglitazone reflected by rat/human hepatocytes ► 3D hepatocytes in 21 days’ long-term culture used for drug hepatotoxicity ► Oversensitive toxicity in hepatocyte monolayer by slow troglitazone clearance.

  11. Sensitivity of screening-level toxicity tests using soils from a former petroleum refinery

    SciTech Connect (OSTI)

    Pauwels, S.; Bureau, J.; Roy, Y.; Allen, B.; Robidoux, P.Y.; Soucy, M.

    1995-12-31

    The authors tested five composite soil samples from a former refinery. The samples included a reference soil (Mineral Oil and Grease, MO and G < 40 ppm), thermally-treated soil, biotreated soil, and two untreated soils. They evaluated toxicity using the earthworm E. foetida, lettuce, cress, barley, Microtox, green algae, fathead minnow, and D. magna. The endpoints measured were lethality, seed germination, root elongation, growth, and bioluminescence. Toxicity, as measured by the number of positive responses, increased as follows: biotreated soil < untreated soil No. 1 < reference soil < thermally-treated soil and untreated soil No. 2. The biotreated soil generated only one positive response, whereas the thermally-treated soil and untreated soil No. 2 generated five positive responses. The most sensitive and discriminant terrestrial endpoint was lettuce root elongation which responded to untreated soil No. 1, thermally-treated soil, and reference soil. The least sensitive was barley seed germination for which no toxicity was detected. The most sensitive and discriminant aquatic endpoint was green algae growth which responded to untreated soil No. 1, thermally-treated soil, and reference soil. The least sensitive was D. magna for which no toxicity was detected. Overall, soil and aqueous extract toxicity was spotty and no consistent patterns emerged to differentiate the five soils. Biotreatment significantly reduced the effects of the contamination. Aqueous toxicity was measured in the reference soil, probably because of the presence of unknown dissolved compounds in the aqueous extract. Finally, clear differences in sensitivity existed among the test species.

  12. Inhibition of aminoacylase 3 protects rat brain cortex neuronal cells from the toxicity of 4-hydroxy-2-nonenal mercapturate and 4-hydroxy-2-nonenal

    SciTech Connect (OSTI)

    Tsirulnikov, Kirill; Abuladze, Natalia; Bragin, Anatol; Brain Research Institute, University of California at Los Angeles, CA 90095 ; Faull, Kym; Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, CA 90095; Pasarow Mass Spectrometry Laboratory, University of California at Los Angeles, CA 90095 ; Cascio, Duilio; Damoiseaux, Robert; Schibler, Matthew J.; Pushkin, Alexander

    2012-09-15

    4-Hydroxy-2-nonenal (4HNE) and acrolein (ACR) are highly reactive neurotoxic products of lipid peroxidation that are implicated in the pathogenesis and progression of Alzheimer's and Parkinson's diseases. Conjugation with glutathione (GSH) initiates the 4HNE and ACR detoxification pathway, which generates the mercapturates of 4HNE and ACR that can be excreted. Prior work has shown that the efficiency of the GSH-dependent renal detoxification of haloalkene derived mercapturates is significantly decreased upon their deacetylation because of rapid transformation of the deacetylated products into toxic compounds mediated by ?-lyase. The enzymes of the GSH-conjugation pathway and ?-lyases are expressed in the brain, and we hypothesized that a similar toxicity mechanism may be initiated in the brain by the deacetylation of 4HNE- and ACR-mercapturate. The present study was performed to identify an enzyme(s) involved in 4HNE- and ACR-mercapturate deacetylation, characterize the brain expression of this enzyme and determine whether its inhibition decreases 4HNE and 4HNE-mercapturate neurotoxicity. We demonstrated that of two candidate deacetylases, aminoacylases 1 (AA1) and 3 (AA3), only AA3 efficiently deacetylates both 4HNE- and ACR-mercapturate. AA3 was further localized to neurons and blood vessels. Using a small molecule screen we generated high-affinity AA3 inhibitors. Two of them completely protected rat brain cortex neurons expressing AA3 from the toxicity of 4HNE-mercapturate. 4HNE-cysteine (4HNE-Cys) was also neurotoxic and its toxicity was mostly prevented by a ?-lyase inhibitor, aminooxyacetate. The results suggest that the AA3 mediated deacetylation of 4HNE-mercapturate may be involved in the neurotoxicity of 4HNE.

  13. TOXIC SUBSTANCES FROM COAL COMBUSTION-A COMPREHENSIVE ASSESSMENT

    SciTech Connect (OSTI)

    C.L. Senior; F. Huggins; G.P. Huffman; N. Shah; N. Yap; J.O.L. Wendt; W. Seames; M.R. Ames; A.F. Sarofim; S. Swenson; J.S. Lighty; A. Kolker; R. Finkelman; C.A. Palmer; S.J. Mroczkowski; J.J. Helble; R. Mamani-Paco; R. Sterling; G. Dunham; S. Miller

    2001-06-30

    The Clean Air Act Amendments of 1990 identify a number of hazardous air pollutants (HAPs) as candidates for regulation. Should regulations be imposed on HAP emissions from coal-fired power plants, a sound understanding of the fundamental principles controlling the formation and partitioning of toxic species during coal combustion will be needed. With support from the National Energy Technology Laboratory (NETL), the Electric Power Research Institute, and VTT (Finland), Physical Sciences Inc. (PSI) has teamed with researchers from USGS, MIT, the University of Arizona (UA), the University of Kentucky (UK), the University of Connecticut (UC), the University of Utah (UU) and the University of North Dakota Energy and Environmental Research Center (EERC) to develop a broadly applicable emissions model useful to regulators and utility planners. The new Toxics Partitioning Engineering Model (ToPEM) will be applicable to all combustion conditions including new fuels and coal blends, low-NOx combustion systems, and new power generation plants. Development of ToPEM will be based on PSI's existing Engineering Model for Ash Formation (EMAF). The work discussed in this report covers the Phase II program. Five coals were studied (three in Phase I and two new ones in Phase II). In this work UK has used XAFS and Moessbauer spectroscopies to characterize elements in project coals. For coals, the principal use was to supply direct information about certain hazardous and other key elements (iron) to complement the more complete indirect investigation of elemental modes of occurrence being carried out by colleagues at USGS. Iterative selective leaching using ammonium acetate, HCl, HF, and HNO3, used in conjunction with mineral identification/quantification, and microanalysis of individual mineral grains, has allowed USGS to delineate modes of occurrence for 44 elements. The Phase II coals show rank-dependent systematic differences in trace-element modes of occurrence. The work at UU

  14. Modifications to toxic CUG RNAs induce structural stability, rescue mis-splicing in a myotonic dystrophy cell model and reduce toxicity in a myotonic dystrophy zebrafish model

    SciTech Connect (OSTI)

    deLorimier, Elaine; Coonrod, Leslie A.; Copperman, Jeremy; Taber, Alex; Reister, Emily E.; Sharma, Kush; Todd, Peter K.; Guenza, Marina G.; Berglund, J. Andrew

    2014-10-10

    In this study, CUG repeat expansions in the 3' UTR of dystrophia myotonica protein kinase (DMPK) cause myotonic dystrophy type 1 (DM1). As RNA, these repeats elicit toxicity by sequestering splicing proteins, such as MBNL1, into proteinRNA aggregates. Structural studies demonstrate that CUG repeats can form A-form helices, suggesting that repeat secondary structure could be important in pathogenicity. To evaluate this hypothesis, we utilized structure-stabilizing RNA modifications pseudouridine (?) and 2'-O-methylation to determine if stabilization of CUG helical conformations affected toxicity. CUG repeats modified with ? or 2'-O-methyl groups exhibited enhanced structural stability and reduced affinity for MBNL1. Molecular dynamics and X-ray crystallography suggest a potential water-bridging mechanism for ?-mediated CUG repeat stabilization. ? modification of CUG repeats rescued mis-splicing in a DM1 cell model and prevented CUG repeat toxicity in zebrafish embryos. This study indicates that the structure of toxic RNAs has a significant role in controlling the onset of neuromuscular diseases.

  15. Modifications to toxic CUG RNAs induce structural stability, rescue mis-splicing in a myotonic dystrophy cell model and reduce toxicity in a myotonic dystrophy zebrafish model

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    deLorimier, Elaine; Coonrod, Leslie A.; Copperman, Jeremy; Taber, Alex; Reister, Emily E.; Sharma, Kush; Todd, Peter K.; Guenza, Marina G.; Berglund, J. Andrew

    2014-10-10

    In this study, CUG repeat expansions in the 3' UTR of dystrophia myotonica protein kinase (DMPK) cause myotonic dystrophy type 1 (DM1). As RNA, these repeats elicit toxicity by sequestering splicing proteins, such as MBNL1, into protein–RNA aggregates. Structural studies demonstrate that CUG repeats can form A-form helices, suggesting that repeat secondary structure could be important in pathogenicity. To evaluate this hypothesis, we utilized structure-stabilizing RNA modifications pseudouridine (Ψ) and 2'-O-methylation to determine if stabilization of CUG helical conformations affected toxicity. CUG repeats modified with Ψ or 2'-O-methyl groups exhibited enhanced structural stability and reduced affinity for MBNL1. Molecular dynamicsmore » and X-ray crystallography suggest a potential water-bridging mechanism for Ψ-mediated CUG repeat stabilization. Ψ modification of CUG repeats rescued mis-splicing in a DM1 cell model and prevented CUG repeat toxicity in zebrafish embryos. This study indicates that the structure of toxic RNAs has a significant role in controlling the onset of neuromuscular diseases.« less

  16. Non-toxic silver iodide (AgI) quantum dots sensitized solar cells

    SciTech Connect (OSTI)

    Moosakhani, S.; Sabbagh Alvani, A.A.; Sarabi, A.A.; Sameie, H.; Salimi, R.; Kiani, S.; Ebrahimi, Y.

    2014-12-15

    Highlights: • We have demonstrated AgI sensitized solar cell for the first time. • Obtained mesoporous titania powders possessed small crystallite size, high purity and surface area, and developed mesopores with a narrow pore size distribution. • Photovoltaic measurements revealed the electron injection from AgI to TiO{sub 2}. • The assembled AgI-QD solar cells yielded a power conversion efficiency of 0.64% under one sun illumination. • AgI may be a suitable candidate material for use as a non-toxic sensitizer in QDSSC. - Abstract: The present study reports the performance of a new photosensitizer -AgI quantum dots (QDs)- and mesoporous titania (TiO{sub 2}) nanocrystals synthesized by sol–gel (SG) method for solar cells. Furthermore, the effects of n-heptane on the textural properties of TiO{sub 2} nanocrystals were comprehensively investigated by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), N{sub 2} adsorption–desorption measurements, and UV–vis spectroscopy. TiO{sub 2} powders exhibited an anatase-type mesoporous structure with a high surface area of 89.7 m{sup 2}/g. Afterwards, the QDs were grown on mesoporous TiO{sub 2} surface to fabricate a TiO{sub 2}/AgI electrode by a successive ionic layer adsorption and reaction (SILAR) deposition route. Current–voltage characteristics and electrochemical impedance spectroscopy (EIS) data demonstrated that the injection of photoexcited electrons from AgI QDs into the TiO{sub 2} matrix produces photocurrents. The assembled AgI-QD solar cells yielded a power conversion efficiency of 0.64% and a short-circuit current of 2.13 mA/cm{sup 2} under one sun illumination.

  17. 2008 Toxic Chemical Release Inventory 2008 Toxic Chemical Release Inventory Community Right-to-Know Act of 1986, Title III, Section 313

    SciTech Connect (OSTI)

    Ecology and Air Quality Group

    2009-10-01

    For reporting year 2008, Los Alamos National Laboratory (LANL) submitted a Form R report for lead as required under the Emergency Planning and Community Right-to- Know Act (EPCRA) Section 313. No other EPCRA Section 313 chemicals were used in 2008 above the reportable thresholds. This document was prepared to provide a description of the evaluation of EPCRA Section 313 chemical use and threshold determinations for LANL for calendar year 2008, as well as to provide background information about data included on the Form R reports. Section 313 of EPCRA specifically requires facilities to submit a Toxic Chemical Release Inventory Report (Form R) to the U.S. Environmental Protection Agency (EPA) and state agencies if the owners and operators manufacture, process, or otherwise use any of the listed toxic chemicals above listed threshold quantities. EPA compiles this data in the Toxic Release Inventory database. Form R reports for each chemical over threshold quantities must be submitted on or before July 1 each year and must cover activities that occurred at the facility during the previous year. In 1999, EPA promulgated a final rule on persistent bioaccumulative toxics (PBTs). This rule added several chemicals to the EPCRA Section 313 list of toxic chemicals and established lower reporting thresholds for these and other PBT chemicals that were already reportable. These lower thresholds became applicable in reporting year 2000. In 2001, EPA expanded the PBT rule to include a lower reporting threshold for lead and lead compounds. Facilities that manufacture, process, or otherwise use more than 100 lb of lead or lead compounds must submit a Form R.

  18. The underlying toxicological mechanism of chemical mixtures: A case study on mixture toxicity of cyanogenic toxicants and aldehydes to Photobacterium phosphoreum

    SciTech Connect (OSTI)

    Tian, Dayong; Lin, Zhifen; Zhou, Xianghong; Yin, Daqiang

    2013-10-15

    Intracellular chemical reaction of chemical mixtures is one of the main reasons that cause synergistic or antagonistic effects. However, it still remains unclear what the influencing factors on the intracellular chemical reaction are, and how they influence on the toxicological mechanism of chemical mixtures. To reveal this underlying toxicological mechanism of chemical mixtures, a case study on mixture toxicity of cyanogenic toxicants and aldehydes to Photobacterium phosphoreum was employed, and both their joint effects and mixture toxicity were observed. Then series of two-step linear regressions were performed to describe the relationships between joint effects, the expected additive toxicities and descriptors of individual chemicals (including concentrations, binding affinity to receptors, octanol/water partition coefficients). Based on the quantitative relationships, the underlying joint toxicological mechanisms were revealed. The result shows that, for mixtures with their joint effects resulting from intracellular chemical reaction, their underlying toxicological mechanism depends on not only their interaction with target proteins, but also their transmembrane actions and their concentrations. In addition, two generic points of toxicological mechanism were proposed including the influencing factors on intracellular chemical reaction and the difference of the toxicological mechanism between single reactive chemicals and their mixtures. This study provided an insight into the understanding of the underlying toxicological mechanism for chemical mixtures with intracellular chemical reaction. - Highlights: Joint effects of nitriles and aldehydes at non-equitoxic ratios were determined. A novel descriptor, ligandreceptor interaction energy (E{sub binding}), was employed. Quantitative relationships for mixtures were developed based on a novel descriptor. The underlying toxic mechanism was revealed based on quantitative relationships. Two generic points of

  19. Scoping analysis of toxic metal performance in DOE low-level waste disposal facilities

    SciTech Connect (OSTI)

    Waters, R.D; Bougai, D.A.; Pohl, P.I.

    1996-03-01

    This study provides a scoping safety assessment for disposal of toxic metals contained in Department of Energy (DOE) mixed low-level waste (MLLW) at six DOE sites that currently have low-level waste (LLW) disposal facilities--Savannah River Site, Oak Ridge Reservation, Los Alamos National Laboratory, Hanford Reservation, Nevada Test Site, and Idaho National Engineering Laboratory. The study has focused on the groundwater contaminant pathway, which is considered to be the dominant human exposure pathway from shallow land MLLW disposal. A simple and conservative transport analysis has been performed using site hydrological data to calculate site-specific ``permissible`` concentrations of toxic metals in grout-immobilized waste. These concentrations are calculated such that, when toxic metals are leached from the disposal facility by infiltrating water and attenuated in local ground-water system the toxic metal concentrations in groundwater below the disposal facility do not exceed the Maximum Contaminant Levels as stated in the National Primary Drinking Water Regulation. The analysis shows that and sites allow about I00 times higher toxic metal concentrations in stabilized waste leachate than humid sites. From the limited available data on toxic metal concentrations in DOE MLLW, a margin of protection appears to exist in most cases when stabilized wastes containing toxic metals are disposed of at the DOE sites under analysis. Possible exceptions to this conclusion are arsenic, chromium selenium, and mercury when disposed of at some humid sites such as the Oak Ridge Reservation. This analysis also demonstrates that the US Environmental Protection Agency`s prescriptive regulatory approach that defines rigid waste treatment standards does not inherently account for the variety of disposal environments encountered nationwide and may result in either underprotection of groundwater resources (at humid sites) or an excessive margin of protection (at and sites).

  20. The effect of exposure to 1,2,4,5-tetrachlorobenzene and the relationship between toxicant and oxygen uptake in rainbow trout (Oncorhynchus mykiss) during exercise

    SciTech Connect (OSTI)

    Brauner, C.J.; Randall, D.J. . Dept. of Zoology); Neuman, J.F.; Thurston, R.V. . Fisheries Bioassay Lab.)

    1994-11-01

    These studies were designed to investigate the relationship between the initial uptake of a model toxicant, 1,2,4,5-tetrachlorobenzene (TCB), and the rate of oxygen consumption (MO[sub 2]) in trout during exercise. There was no effect of environmental TCB concentrations ([TCB]) on the MO[sub 2] of resting or exercising adult rainbow trout, and body accumulations of the toxicant did not affect the maximal aerobic swimming velocity attained by juvenile rainbow trout. Rainbow trout were exposed to TCB for 1 h while swimming at different velocities and the [TCB] was measured in plasma and 11 other tissues. Tissue TCB concentrations were found to be extremely variable despite similar exposure conditions, likely due to differences in tissue lipid content. No one tissue was representative of body burden, but tissue TCB delivery appears to be directly related to the [TCB] in the plasma because at different swimming velocities the plasma:tissue TCB ratios remained constant despite regional changes in blood flow. After 2 h of TCB exposure, [TCB] in the plasma was equal to whole-body [TCB]; however, this relationship broke down after 6 h. Thus, whole-body TCB concentrations can only be obtained through direct measurement. There was a highly significant relationship between MO[sub 2] and TCB uptake rate during initial toxicant exposure in adult rainbow trout forced to swim over a large proportion of its aerobic potential. Thus, toxicant uptake in fish may be estimated based upon MO[sub 2], which can be measured or can be obtained from the literature.

  1. Acute toxicity and aqueous solubility of some condensed thiophenes and their microbial metabolites

    SciTech Connect (OSTI)

    Seymour, D.T.; Hrudey, S.E.; Fedorak, P.M.; Verbeek, A.G.

    1997-04-01

    Petroleum or creosote contamination of surface waters, soils, or groundwaters introduces countless aromatic compounds to these environments. Among these are condensed thiophenes that were shown to be oxidized to sulfoxides, sulfones, and 2,3-diones by microbial cultures. In this study, the acute toxicities of 12 compounds (benzothiophene, benzothiophene sulfone, benzothiophene-2,3-diones, dibenzothiophene, dibenzothiophene sulfoxide, and dibenzothiophene sulfone) were determined by the Microtox{reg_sign} and Daphnia magna bioassays. To aid in determining the toxicities, the solubilities of many of these compounds were determined, which showed that the oxidized compounds were much more water soluble than the parent thiophenes. In nearly every case, the oxidized compounds were less toxic than their parent thiophenes. The Microtox method was more sensitive than the D. magna bioassay, but in general, there was a good correlation between toxicities measured by the two tests. Samples were removed from batch cultures of a Pseudomonas strain capable of oxidizing the thiophenes, and these samples were subjected to Microtox bioassays. These experiments showed that the toxicities of the culture supernatants decreased with incubation time.

  2. Old, the new, the states, the evolution of the regulation of air toxics. Master's thesis

    SciTech Connect (OSTI)

    Vecera, D.R.

    1993-02-14

    The activism associated with America in the 1960s spilled over into many areas, one of which was a new environmental movement. A product of that movement was the Clean Air Act passed in 1970. The new law included a selection aimed specifically at controlling emissions of hazardous or toxic air pollutants. However, over the next 20 years there was very little government regulation of air toxics, and this section of the Clean Air Act was considered to be a resounding failure. What went wrong. How did this lofty goal to protect human health and the environment end up on the back burner. The article will address the idealism that led to the Clean Air Act legislation, in particular the air toxics program, and explore the realities that scuttled those ideals when it came time to implement the law.

  3. Random Forests to Predict Rectal Toxicity Following Prostate Cancer Radiation Therapy

    SciTech Connect (OSTI)

    Ospina, Juan D.; Zhu, Jian; Chira, Ciprian; Bossi, Alberto; Delobel, Jean B.; Beckendorf, Véronique; Dubray, Bernard; Lagrange, Jean-Léon; Correa, Juan C.; and others

    2014-08-01

    Purpose: To propose a random forest normal tissue complication probability (RF-NTCP) model to predict late rectal toxicity following prostate cancer radiation therapy, and to compare its performance to that of classic NTCP models. Methods and Materials: Clinical data and dose-volume histograms (DVH) were collected from 261 patients who received 3-dimensional conformal radiation therapy for prostate cancer with at least 5 years of follow-up. The series was split 1000 times into training and validation cohorts. A RF was trained to predict the risk of 5-year overall rectal toxicity and bleeding. Parameters of the Lyman-Kutcher-Burman (LKB) model were identified and a logistic regression model was fit. The performance of all the models was assessed by computing the area under the receiving operating characteristic curve (AUC). Results: The 5-year grade ≥2 overall rectal toxicity and grade ≥1 and grade ≥2 rectal bleeding rates were 16%, 25%, and 10%, respectively. Predictive capabilities were obtained using the RF-NTCP model for all 3 toxicity endpoints, including both the training and validation cohorts. The age and use of anticoagulants were found to be predictors of rectal bleeding. The AUC for RF-NTCP ranged from 0.66 to 0.76, depending on the toxicity endpoint. The AUC values for the LKB-NTCP were statistically significantly inferior, ranging from 0.62 to 0.69. Conclusions: The RF-NTCP model may be a useful new tool in predicting late rectal toxicity, including variables other than DVH, and thus appears as a strong competitor to classic NTCP models.

  4. The possibility of garbage, medical and other toxic waste treatment by plasma chemical method

    SciTech Connect (OSTI)

    Rutberg, P.G.; Safronov, A.A.; Bratsev, A.N.; Kuznetsov, V.E.

    1998-12-31

    This paper describes the creation of plasma facility for treatment of toxic waste. All industrialized countries are greatly interested in plasma chemical technology application for the destruction of different types of industrial, building, purification works toxic waste and waste of plants for garbage treatment. On the basis of three-phase plasma generators with power 0.1--1 MW intended for work in air a row of pilot facilities were created for carrying out of experiments on destruction of medical waste and fluorine-chlorine containing substances. The obtained results allow to design and create pilot-commercial plants with treatment productivity of 200 t/24 hours.

  5. Method for screening inhibitors of the toxicity of Bacillus anthracis

    DOE Patents [OSTI]

    Cirino, Nick M.; Jackson, Paul J.; Lehnert, Bruce E.

    2001-01-01

    The protective antigen (PA) of Bacillus anthracis is integral to the mechanism of anthrax poisoning. The cloning, expression and purification of a 32 kDa B. anthracis PA fragment (PA32) is described. This fragment has also been expressed as a fusion construct to stabilized green fluorescent protein (EGFP-PA32). Both proteins were capable of binding to specific cell surface receptors as determined by fluorescent microscopy and a flow cytometric assay. To confirm binding specificity in the flow cytometric assay, non-fluorescent PA83 or PA32 was used to competitively inhibit fluorescent EGFP-PA32 binding to cell receptors. This assay can be employed as a rapid screen for compounds which disrupts binding of PA to cells. Additionally, the high intracellular expression levels and ease of purification make this recombinant protein an attractive vaccine candidate or therapeutic treatment for anthrax poisoning.

  6. Toxic substances from coal combustion -- A comprehensive assessment

    SciTech Connect (OSTI)

    Senior, C.L.; Huggins, F.E.; Huffman, G.P.; Shan, N.; Yap, N.; Wendt, J.O.L.; Seames, W.; Ames, M.R.; Sarofim, A.F.; Swenson, S.; Lighty, J.; Kolker, A.; Finkelman, R.; Palmer, C.; Mroczkowski, S.; Helble, J.; Mamani-Paco, R.; Sterling, R.; Dunham, G.; Miller, S.

    2000-08-17

    The final program review meeting of Phase II was held on June 22 in Salt Lake City. The goals of the meeting were to present work in progress and to identify the remaining critical experiments or analyses, particularly those involving collaboration among various groups. The information presented at the meeting is summarized in this report. Remaining fixed bed, bench-scale experiments at EERC were discussed. There are more ash samples which can be run. Of particular interest are high carbon ash samples to be generated by the University of Arizona this summer and some ash-derived sorbents that EERC has evaluated on a different program. The use of separation techniques (electrostatic or magnetic) was also discussed as a way to understand the active components in the ash with respect to mercury. XAFS analysis of leached and unleached ash samples from the University of Arizona was given a high priority. In order to better understand the fixed bed test results, CCSEM and Moessbauer analyses of those ash samples need to be completed. Utah plans to analyze the ash from the single particle combustion experiments for those major elements not measured by INAA. USGS must still complete mercury analyses on the whole coals and leaching residues. Priorities for further work at the SHRIMP-RG facility include arsenic on ash surfaces and mercury in sulfide minerals. Moessbauer analyses of coal samples from the University of Utah were completed; samples from the top and bottom layers of containers of five different coals showed little oxidation of pyrite in the top relative to the bottom except for Wyodak.

  7. In silico prediction of toxicity of non-congeneric industrial chemicals using ensemble learning based modeling approaches

    SciTech Connect (OSTI)

    Singh, Kunwar P. Gupta, Shikha

    2014-03-15

    Ensemble learning approach based decision treeboost (DTB) and decision tree forest (DTF) models are introduced in order to establish quantitative structuretoxicity relationship (QSTR) for the prediction of toxicity of 1450 diverse chemicals. Eight non-quantum mechanical molecular descriptors were derived. Structural diversity of the chemicals was evaluated using Tanimoto similarity index. Stochastic gradient boosting and bagging algorithms supplemented DTB and DTF models were constructed for classification and function optimization problems using the toxicity end-point in T. pyriformis. Special attention was drawn to prediction ability and robustness of the models, investigated both in external and 10-fold cross validation processes. In complete data, optimal DTB and DTF models rendered accuracies of 98.90%, 98.83% in two-category and 98.14%, 98.14% in four-category toxicity classifications. Both the models further yielded classification accuracies of 100% in external toxicity data of T. pyriformis. The constructed regression models (DTB and DTF) using five descriptors yielded correlation coefficients (R{sup 2}) of 0.945, 0.944 between the measured and predicted toxicities with mean squared errors (MSEs) of 0.059, and 0.064 in complete T. pyriformis data. The T. pyriformis regression models (DTB and DTF) applied to the external toxicity data sets yielded R{sup 2} and MSE values of 0.637, 0.655; 0.534, 0.507 (marine bacteria) and 0.741, 0.691; 0.155, 0.173 (algae). The results suggest for wide applicability of the inter-species models in predicting toxicity of new chemicals for regulatory purposes. These approaches provide useful strategy and robust tools in the screening of ecotoxicological risk or environmental hazard potential of chemicals. - Graphical abstract: Importance of input variables in DTB and DTF classification models for (a) two-category, and (b) four-category toxicity intervals in T. pyriformis data. Generalization and predictive abilities of the

  8. Insights into Acetate Toxicity in Zymomonas mobilis 8b using Different Substrates

    SciTech Connect (OSTI)

    Yang, Shihui; Franden, M. A.; Brown, S. D.; Chou, Y. C.; Pienkos, P. T.; Zhang, Min

    2014-09-30

    The lignocellulosic biomass is a promising renewable feedstock for biofuel production. Acetate is one of the major inhibitors liberated from hemicelluloses during hydrolysis. Likewise, an understanding of the toxic effects of acetate on the fermentation microorganism and the efficient utilization of mixed sugars of glucose and xylose in the presence of hydrolysate inhibitors is crucial for economic biofuel production.

  9. Lethal body concentrations and accumulation patterns determine time-dependent toxicity of cadmium in soil arthropods

    SciTech Connect (OSTI)

    Crommentuijn, T.; Doodeman, C.J.A.M.; Doornekamp, A.; Pol, J.J.C. van der; Bedaux, J.J.M.; Gestel, C.A.M. van )

    1994-11-01

    Time-dependent toxicity in bioassays is usually explained in terms of uptake and elimination kinetics of the toxicant. By comparing different species with essentially different accumulation kinetics, a firm test of this concept may be made. This article compares the sensitivity of six soil arthropods, the collembolans Orchesella cincta and Tomocerus minor, the oribatid mite Platynothrus peltifer, the isopods Porcellio scaber and Oniscus asellus, and the diplopod Cylindroiulus britannicus, when exposed to cadmium in the food. Survival was determined at various time intervals; accumulation of cadmium in the animals was measured at one time interval. Kinetic-based toxicity models were fitted to the data, and estimates were obtained for lethal body concentration, uptake rate constant, elimination rate constant, and ultimate LC50. Two different accumulation patterns could be discerned; these were correlated with time-survival relationships. One, species that have the possibility to eliminate cadmium will reach an equilibrium for the internal concentration and also an ultimate LC50. Two, species that are unable to eliminate cadmium but store it in the body will have an ultimate LC50 equal to zero. For these species the time in which the lethal body concentration is reached is more important. Taxonomically related species appeared to have comparable accumulation patterns, but lethal body concentrations differed. It is concluded that knowledge of the accumulation pattern is indispensable for the evaluation of species' sensitivities to toxicants.

  10. Plant toxicity studies made publicly available by EPA and the TSCA Interagency Testing Committee

    SciTech Connect (OSTI)

    Walker, J.D.

    1994-12-31

    The purpose of this presentation is to briefly describe the ITC, describe the Toxic Substances Control Act (TSCA) Test Submissions (TSCATS) database and how the EPA makes unpublished health and safety studies publicly available through TSCATS as a result of ITC testing recommendations and other activities and to describe some of the unpublished plant toxicity studies that are available tin TSCATS. In 1976, under section 4(e) of the Toxic Substances Control Act (TSCA), the US Congress created the ITC to implement the initial phases of testing TSCA-regulable chemicals. Congress directed the ITC to: (1) make testing decisions on about 70,000 chemicals, (2) develop the TSCA Section 4(e) Priority Testing List, (3) coordinate chemical testing and (4) revise the List at least every six months. The creation, structure, functions and contributions of the ITC from 1977 to 1992 have been previously described. TSCATS is an EPA database. It is an online pointer file that identifies all the unpublished studies that have been submitted to EPA under TSCA sections 4 and 8 and as For Your Information studies. Most of the studies in TSCATS were submitted by manufacturers of chemicals that ITC has added to the Priority Testing List because EPA has published Federal Register notices requesting that manufacturers of ITC chemicals submit unpublished data under TSCA section 8 or conduct testing and submit the data that were developed under TSCA section 4. Data from plant toxicity studies indexed in TSCATS will be presented.

  11. The risk of lead toxicity in homes with lead paint hazard

    SciTech Connect (OSTI)

    Schwartz, J.; Levin, R. )

    1991-02-01

    While lead paint has long been known to be a major source of lead poisoning, only a few small epidemiologic studies have attempted to assess directly the relative risk of lead poisoning due to the presence of lead paint. Using data from over 200,000 screening tests of children in the city of Chicago performed between 1976 and 1980, the relative risks can be quantified for children living in a major urban area. Lead paint was found to be a significant predictor of the probability of a child having lead toxicity. As expected, the reduction in leaded gasoline sales during the period reduced mean blood lead levels and increased the percentage of lead toxic children whose toxicity could be attributed to paint lead. Poisson regression models indicated that with the elimination of leaded gasoline, the relative risk of lead toxicity given lead paint exposure was 5.70 (95% CI, 4.13-7.86) during the winter and fall. The relative risk rose to 12.81 (95% CI, 7.33-22.4) in the spring and 15.8 (95% CI, 8.90-28.1) in the summer, probably due to increased exposure to window wells.

  12. Pulmonary toxicity after exposure to military-relevant heavy metal tungsten alloy particles

    SciTech Connect (OSTI)

    Roedel, Erik Q.; Cafasso, Danielle E.; Lee, Karen W.M.; Pierce, Lisa M.

    2012-02-15

    Significant controversy over the environmental and public health impact of depleted uranium use in the Gulf War and the war in the Balkans has prompted the investigation and use of other materials including heavy metal tungsten alloys (HMTAs) as nontoxic alternatives. Interest in the health effects of HMTAs has peaked since the recent discovery that rats intramuscularly implanted with pellets containing 91.1% tungsten/6% nickel/2.9% cobalt rapidly developed aggressive metastatic tumors at the implantation site. Very little is known, however, regarding the cellular and molecular mechanisms associated with the effects of inhalation exposure to HMTAs despite the recognized risk of this route of exposure to military personnel. In the current study military-relevant metal powder mixtures consisting of 92% tungsten/5% nickel/3% cobalt (WNiCo) and 92% tungsten/5% nickel/3% iron (WNiFe), pure metals, or vehicle (saline) were instilled intratracheally in rats. Pulmonary toxicity was assessed by cytologic analysis, lactate dehydrogenase activity, albumin content, and inflammatory cytokine levels in bronchoalveolar lavage fluid 24 h after instillation. The expression of 84 stress and toxicity-related genes was profiled in lung tissue and bronchoalveolar lavage cells using real-time quantitative PCR arrays, and in vitro assays were performed to measure the oxidative burst response and phagocytosis by lung macrophages. Results from this study determined that exposure to WNiCo and WNiFe induces pulmonary inflammation and altered expression of genes associated with oxidative and metabolic stress and toxicity. Inhalation exposure to both HMTAs likely causes lung injury by inducing macrophage activation, neutrophilia, and the generation of toxic oxygen radicals. -- Highlights: ► Intratracheal instillation of W–Ni–Co and W–Ni–Fe induces lung inflammation in rats. ► W–Ni–Co and W–Ni–Fe alter expression of oxidative stress and toxicity genes. ► W

  13. Age and Comorbid Illness Are Associated With Late Rectal Toxicity Following Dose-Escalated Radiation Therapy for Prostate Cancer

    SciTech Connect (OSTI)

    Hamstra, Daniel A.; Stenmark, Matt H.; Ritter, Tim; Litzenberg, Dale; Jackson, William; Johnson, Skyler; Albrecht-Unger, Liesel; Donaghy, Alex; Phelps, Laura; Blas, Kevin; Halverson, Schuyler; Marsh, Robin; Olson, Karin; Feng, Felix Y.

    2013-04-01

    Purpose: To assess the impacts of patient age and comorbid illness on rectal toxicity following external beam radiation therapy (EBRT) for prostate cancer and to assess the Qualitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) normal tissue complication probability (NTCP) model in this context. Methods and Materials: Rectal toxicity was analyzed in 718 men previously treated for prostate cancer with EBRT (≥75 Gy). Comorbid illness was scored using the Charlson Comorbidity Index (CCMI), and the NTCP was evaluated with the QUANTEC model. The influence of clinical and treatment-related parameters on rectal toxicity was assessed by Kaplan-Meier and Cox proportional hazards models. Results: The cumulative incidence of rectal toxicity grade ≥2 was 9.5% and 11.6% at 3 and 5 years and 3.3% and 3.9% at 3 and 5 years for grade ≥3 toxicity, respectively. Each year of age predicted an increasing relative risk of grade ≥2 (P<.03; hazard ratio [HR], 1.04 [95% confidence interval (CI), 1.01-1.06]) and ≥3 rectal toxicity (P<.0001; HR, 1.14 [95% CI,1.07-1.22]). Increasing CCMI predicted rectal toxicity where a history of either myocardial infarction (MI) (P<.0001; HR, 5.1 [95% CI, 1.9-13.7]) or congestive heart failure (CHF) (P<.0006; HR, 5.4 [95% CI, 0.6-47.5]) predicted grade ≥3 rectal toxicity, with lesser correlation with grade ≥2 toxicity (P<.02 for MI, and P<.09 for CHF). An age comorbidity model to predict rectal toxicity was developed and confirmed in a validation cohort. The use of anticoagulants increased toxicity independent of age and comorbidity. NTCP was prognostic for grade ≥3 (P=.015) but not grade ≥2 (P=.49) toxicity. On multivariate analysis, age, MI, CHF, and an NTCP >20% all correlated with late rectal toxicity. Conclusions: Patient age and a history of MI or CHF significantly impact rectal toxicity following EBRT for the treatment of prostate cancer, even after controlling for NTCP.

  14. Hypopharyngeal Dose Is Associated With Severe Late Toxicity in Locally Advanced Head-and-Neck Cancer: An RTOG Analysis

    SciTech Connect (OSTI)

    Machtay, Mitchell; Moughan, Jennifer; Farach, Andrew; University of Texas Health Science Center Martin-O'Meara, Elizabeth; Galvin, James; Thomas Jefferson University, Philadelphia, Pennsylvania ; Garden, Adam S.; Weber, Randal S.; Cooper, Jay S.; Forastiere, Arlene; Ang, K. Kian

    2012-11-15

    Purpose: Concurrent chemoradiation therapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN) increases local tumor control but at the expense of increased toxicity. We recently showed that several clinical/pretreatment factors were associated with the occurrence of severe late toxicity. This study evaluated the potential relationship between radiation dose delivered to the pharyngeal wall and toxicity. Methods and Materials: This was an analysis of long-term survivors from 3 previously reported Radiation Therapy Oncology Group (RTOG) trials of CCRT for locally advanced SCCHN (RTOG trials 91-11, 97-03, and 99-14). Severe late toxicity was defined in this secondary analysis as chronic grade 3-4 pharyngeal/laryngeal toxicity and/or requirement for a feeding tube {>=}2 years after registration and/or potential treatment-related death (eg, pneumonia) within 3 years. Radiation dosimetry (2-dimensional) analysis was performed centrally at RTOG headquarters to estimate doses to 4 regions of interest along the pharyngeal wall (superior oropharynx, inferior oropharynx, superior hypopharynx, and inferior hypopharynx). Case-control analysis was performed with a multivariate logistic regression model that included pretreatment and treatment potential factors. Results: A total of 154 patients were evaluable for this analysis, 71 cases (patients with severe late toxicities) and 83 controls; thus, 46% of evaluable patients had a severe late toxicity. On multivariate analysis, significant variables correlated with the development of severe late toxicity, including older age (odds ratio, 1.062 per year; P=.0021) and radiation dose received by the inferior hypopharynx (odds ratio, 1.023 per Gy; P=.016). The subgroup of patients receiving {<=}60 Gy to the inferior hypopharynx had a 40% rate of severe late toxicity compared with 56% for patients receiving >60 Gy. Oropharyngeal dose was not associated with this outcome. Conclusions: Severe late toxicity following CCRT is

  15. High PRF high current switch

    DOE Patents [OSTI]

    Moran, Stuart L.; Hutcherson, R. Kenneth

    1990-03-27

    A triggerable, high voltage, high current, spark gap switch for use in pu power systems. The device comprises a pair of electrodes in a high pressure hydrogen environment that is triggered by introducing an arc between one electrode and a trigger pin. Unusually high repetition rates may be obtained by undervolting the switch, i.e., operating the trigger at voltages much below the self-breakdown voltage of the device.

  16. Sprague-Dawley rats display metabolism-mediated sex differences in the acute toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)

    SciTech Connect (OSTI)

    Fonsart, Julien [Universite Paris Descartes, Faculte de Pharmacie, Paris F-75006 (France)]|[CNRS, UMR 7157, Paris F-75006 (France)]|[INSERM, U705, Paris F-75006 (France); Menet, Marie-Claude [Universite Paris Descartes, Faculte de Pharmacie, Paris F-75006 (France)]|[Universite Paris Descartes, Faculte de Pharmacie, Plateau Spectrometrie de Masse (IFR 71), Service de Chimie Analytique, Paris F-75006 (France); Decleves, Xavier [Universite Paris Descartes, Faculte de Pharmacie, Paris F-75006 (France)]|[CNRS, UMR 7157, Paris F-75006 (France)]|[INSERM, U705, Paris F-75006 (France); Galons, Herve [Universite Paris Descartes, Faculte de Pharmacie, Paris F-75006 (France)]|[INSERM, U648, Paris F-75006 (France); Crete, Dominique; Debray, Marcel; Scherrmann, Jean-Michel [Universite Paris Descartes, Faculte de Pharmacie, Paris F-75006 (France)]|[CNRS, UMR 7157, Paris F-75006 (France)]|[INSERM, U705, Paris F-75006 (France); Noble, Florence [Universite Paris Descartes, Faculte de Pharmacie, Paris F-75006 (France)]|[CNRS, UMR 7157, Paris F-75006 (France)]|[INSERM, U705, Paris F-75006 (France)], E-mail: florence.noble@univ-paris5.fr

    2008-07-01

    The use of the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has been associated with unexplained deaths. Male humans and rodents are more sensitive to acute toxicity than are females, including a potentially lethal hyperthermia. MDMA is highly metabolized to five main metabolites, by the enzymes CYP1A2 and CYP2D. The major metabolite in rats, 3,4-methylenedioxyamphetamine (MDA), also causes hyperthermia. We postulated that the reported sex difference in rats is due to a sexual dimorphism(s). We therefore determined (1) the LD50 of MDMA and MDA, (2) their hyperthermic effects, (3) the activities of liver CYP1A2 and CYP2D, (4) the liver microsomal metabolism of MDMA and MDA, (5) and the plasma concentrations of MDMA and its metabolites 3 h after giving male and female Sprague-Dawley (SD) rats MDMA (5 mg.kg{sup -1} sc). The LD50 of MDMA was 2.4-times lower in males than in females. MDMA induced greater hyperthermia (0.9 deg. C) in males. The plasma MDA concentration was 1.3-fold higher in males, as were CYP1A2 activity (twice) and N-demethylation to MDA (3.3-fold), but the plasma MDMA concentration (1.4-fold) and CYP2D activity (1.3-fold) were higher in females. These results suggest that male SD rats are more sensitive to MDMA acute toxicity than are females, probably because their CYP1A2 is more active, leading to higher N-demethylation and plasma MDA concentration. This metabolic pathway could be responsible for the lethality of MDMA, as the LD50 of MDA is the same in both sexes. These data strongly suggest that the toxicity of amphetamine-related drugs largely depends on metabolic differences.

  17. Model studies in cytochrome P-450 mediated toxicity of halogenated compounds: radical processes involving iron porphyrins

    SciTech Connect (OSTI)

    Brault, D.

    1985-12-01

    Haloalkane toxicity originates from attack on biological targets by reactive intermediates derived from haloalkane metabolism by a hemoprotein, cytochrome P-450. Carbon-centered radicals and their peroxylderivatives are most likely involved. The reactions of iron porphyrin - a model for cytochrome P-450 - with various carbon-centered and peroxyl radicals generated by pulse radiolysis are examined. Competition between iron porphyrin and unsaturated fatty acids for attack by peroxyl radicals is pointed out. These kinetic data are used to derive a model for toxicity of haloalkanes with particular attention to carbon tetrachloride and halothane. The importance of local oxygen concentration and structural arrangement of fatty acids around cytochrome P-450 is emphasized. 56 references.

  18. Attempt to estimate measurement uncertainty in the Air Force Toxic Chemical Dispersion (AFTOX) model. Master's thesis

    SciTech Connect (OSTI)

    Zettlemoyer, M.D.

    1990-01-01

    The Air Force Toxic Chemical Dispersion (AFTOX) model is a Gaussian puff dispersion model that predicts plumes, concentrations, and hazard distances of toxic chemical spills. A measurement uncertainty propagation formula derived by Freeman et al. (1986) is used within AFTOX to estimate resulting concentration uncertainties due to the effects of data input uncertainties in wind speed, spill height, emission rate, and the horizontal and vertical Gaussian dispersion parameters, and the results are compared to true uncertainties as estimated by standard deviations computed by Monte Carlo simulations. The measurement uncertainty uncertainty propagation formula was found to overestimate measurement uncertainty in AFTOX-calculated concentrations by at least 350 percent, with overestimates worsening with increasing stability and/or increasing measurement uncertainty.

  19. Resistance and resilience of pond and stream ecosystems to toxicant stress: Project summary

    SciTech Connect (OSTI)

    Boston, H.L.; Stewart, A.J.; Johnson, A.R.; Bartell, S.M.

    1987-01-01

    This project will evaluate hypotheses concerning the resistance and resilience of aquatic ecosystems exposed to toxic chemicals. Our goals are to develop diagnostic criteria for ecosystem classification and to improve existing methods of ecological risk estimation. The development of models that predict ecosystem level effects requires quantifying the relationships between the underlying control structure of ecosystems (patterns of energy and material flux) and the contributions of thos structures to ecosystem resistance and resilience. We address these problems through an integration of manipulative experiments, multidimensional state space analysis, and ecosystem modeling. These studies will quantify the underlying rate structure in pond and stream systems (including, production, herbivory, nutrient uptake and recycling) and will measure changes in their structures in response to perturbations by toxicants.

  20. Hanford Waste Vitrification Plant technical background document for toxics best available control technology demonstration

    SciTech Connect (OSTI)

    1992-10-01

    This document provides information on toxic air pollutant emissions to support the Notice of Construction for the proposed Hanford Waste Vitrification Plant (HWVP) to be built at the the Department of Energy Hanford Site near Richland, Washington. Because approval must be received prior to initiating construction of the facility, state and federal Clean Air Act Notices of construction are being prepared along with necessary support documentation.

  1. Identifying Biomarkers and Mechanisms of Toxic Metal Stress with Global Proteomics

    SciTech Connect (OSTI)

    Miller, Susan M.

    2012-04-16

    Hg is a wide-spread contaminant in the environment and is toxic in all of its various forms. Data suggest that RHg+ and Hg2+ are toxic in two ways. At low levels, Hg species appear to disrupt membrane-bound respiration causing a burst of reactive oxygen species (ROS) that further damage the cell. At higher Hg concentrations, RHg+ and Hg2+ may form adducts with cysteine- and selenocysteine-containing proteins in all cellular compartments resulting in their inactivation. Although these mechansims for toxicity are generally accepted, the most sensitive targets associated with these mechanisms are not well understood. In this collaborative project involving three laboratories at three institutions, the overall goal was to develop of a mass spectrometry-based global proteomics methodology that could be used to identify Hg-adducted (and ideally, ROS-damaged) proteins in order to address these types of questions. The two objectives of this overall collaborative project were (1) to identify, quantify, and compare ROS- and Hg-damaged proteins in cells treated with various Hg species and concentrations to test this model for two mechanisms of Hg toxicity, and (2) to define the cellular roles of the ubiquitous bacterial mercury resistance (mer) locus with regards to how the proteins of this pathway interact to protect other cell proteins from Hg damage. The specific objectives and accomplishments of the Miller lab in this project included: (1) Development of algorithms for analysis of the Hg-proteomic mass spectrometry data to identify mercury adducted peptides and other trends in the data. (2) Investigation of the role of mer operon proteins in scavenging Hg(II) from other mer pathway proteins as a means of protecting cellular proteins from damage.

  2. Ligand-specific transcriptional mechanisms underlie aryl hydrocarbon receptor-mediated developmental toxicity of oxygenated PAHs

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Goodale, B. C.; Geisel School of Medicine at Dartmouth, Hanover, NH; La Du, J.; Tilton, S. C.; Pacific Northwest National Lab.; Sullivan, C. M.; Bisson, W. H.; Waters, K. M.; Tanguay, R. L.

    2015-07-03

    Polycyclic aromatic hydrocarbons (PAHs) are priority environmental contaminants that exhibit mutagenic, carcinogenic, proinflammatory, and teratogenic properties. Oxygen-substituted PAHs (OPAHs) are formed during combustion processes and via phototoxidation and biological degradation of parent (unsubstituted) PAHs. Despite their prevalence both in contaminated industrial sites and in urban air, OPAH mechanisms of action in biological systems are relatively understudied. Like parent PAHs, OPAHs exert structure-dependent mutagenic activities and activation of the aryl hydrocarbon receptor (AHR) and cytochrome p450 metabolic pathway. Four-ring OPAHs 1,9-benz-10-anthrone (BEZO) and benz(a)anthracene-7,12-dione (7,12-B[a]AQ) cause morphological aberrations and induce markers of oxidative stress in developing zebrafish with similar potency, butmore » only 7,12-B[a]AQ induces robust Cyp1a protein expression. We investigated the role of the AHR in mediating the toxicity of BEZO and 7,12-B[a]AQ, and found that knockdown of AHR2 rescued developmental effects caused by both compounds. Using RNA-seq and molecular docking, we identified transcriptional responses that precede developmental toxicity induced via differential interaction with AHR2. Redox-homeostasis genes were affected similarly by these OPAHs, while 7,12-B[a]AQ preferentially activated phase 1 metabolism and BEZO uniquely decreased visual system genes. Analysis of biological functions and upstream regulators suggests that BEZO is a weak AHR agonist, but interacts with other transcriptional regulators to cause developmental toxicity in an AHR-dependent manner. Furthermore, identifying ligand-dependent AHR interactions and signaling pathways is essential for understanding toxicity of this class of environmentally relevant compounds.« less

  3. Toxic Substances From Coal Combustion - Phase I Coal Selection and Chaacterization

    SciTech Connect (OSTI)

    A. Kolker; A. Sarofim; C.A. Palmer; C.L. Senior; F.E. Huggins; G.P. Huffman; I. Olmez; N. Shah; R. Finkelman; S. Crowley; T. Zeng

    1998-07-16

    The Clean Air Act Amendments of 1990 identify a number of hazardous air pollutants (HAPs) as candidates for regulation. Should regulations be imposed on HAP emissions from coal-fired power plants, a sound understanding of the fundamental principles controlling the formation and partitioning of toxic species during coal combustion will be needed. Over the past decade, a large database identifying the partitioning and emitted concentrations of several toxic metals on the list of HAPs has been developed. Laboratory data have also been generated to help define the general behavior of several elements in combustion systems. These data have been used to develop empirical and probabalistic models to predict emissions of trace metals from coal-fired power plants. While useful for providing average emissions of toxic species, these empirically based models fail when extrapolated beyond their supporting database. This represents a critical gap; over the coming decades, new fuels and combustion systems will play an increasing role in our nation's power generation system. For example, new fuels, such as coal blends or beneficiated fuels, new operating conditions, such as low-NO burners or staged combustion, or new power x systems, for example, those being developed under the DoE sponsored Combustion 2000 programs and integrated gasification combined cycle (IGCC) systems, are all expected to play a role in power generation in the next century. The need for new predictive tools is not limited to new combustion systems, however. Existing combustion systems may have to employ controls for HAPs, should regulations be imposed. Testing of new control methods, at pilot and full scale, is expensive. A sound under-standing of the chemical transformations of both organic and inorganic HAPs will promote the development of new control methods in a cost-effective manner. To ensure that coal-fired power generation proceeds in an environmentally benign fashion, methods for the prediction and

  4. Toxic Substances Control Act Polychlorinated Biphenyls (PCB) Hanford Site Users Guide

    SciTech Connect (OSTI)

    PRIGNANO, A.L.

    2002-01-01

    The U.S Department of Energy, Richland Operations Office and the Office of River Protection, requested the development of an integrated and consistent approach to management of polychlorinated biphenyls on the Hanford Site. Under their respective contracts, the Hanford Site contractors are required to comply with polychlorinated biphenyl regulations under the Toxic Substances Control Act of 1976. The objective of this Toxic Substances Control Act Polychlorinated Biphenyls Hanford Site Users Guide is to establish consistent guidance for use by Hanford Site contractors for managing polychlorinated biphenyls. Polychlorinated biphenyls have been identified in some Hanford Site waste, and based on the experiences of the rest of the US. Department of Energy Complex, polychlorinated biphenyls could be expected to be found in an even wider variety of waste. Because of the unique and often cumbersome regulatory requirements that apply to management of polychlorinated biphenyls and polychlorinated biphenyl contaminated materials, the U.S. Department of Energy instructed the contractors to use a proactive approach to develop a Polychlorinated Biphenyls Hanford Site User's Guide to ensure an integrated and consistent approach to management of Toxic Substances Control Act regulated polychlorinated biphenyls in the most cost-effective and compliant manner. Implementation of Toxic Substances Control Act regulated polychlorinated biphenyl requirements on the Hanford Site is accomplished through three paths. One path is the application of the regulations as written to the management of waste contaminated with polychlorinated biphenyls. The U.S. Environmental Protection Agency provides clarification to the regulations through a series of technical references posted on their web site and via questions and answers for the regulated community.

  5. Ligand-specific transcriptional mechanisms underlie aryl hydrocarbon receptor-mediated developmental toxicity of oxygenated PAHs

    SciTech Connect (OSTI)

    Goodale, B. C.; La Du, J.; Tilton, S. C.; Sullivan, C. M.; Bisson, W. H.; Waters, K. M.; Tanguay, R. L.

    2015-07-03

    Polycyclic aromatic hydrocarbons (PAHs) are priority environmental contaminants that exhibit mutagenic, carcinogenic, proinflammatory, and teratogenic properties. Oxygen-substituted PAHs (OPAHs) are formed during combustion processes and via phototoxidation and biological degradation of parent (unsubstituted) PAHs. Despite their prevalence both in contaminated industrial sites and in urban air, OPAH mechanisms of action in biological systems are relatively understudied. Like parent PAHs, OPAHs exert structure-dependent mutagenic activities and activation of the aryl hydrocarbon receptor (AHR) and cytochrome p450 metabolic pathway. Four-ring OPAHs 1,9-benz-10-anthrone (BEZO) and benz(a)anthracene-7,12-dione (7,12-B[a]AQ) cause morphological aberrations and induce markers of oxidative stress in developing zebrafish with similar potency, but only 7,12-B[a]AQ induces robust Cyp1a protein expression. We investigated the role of the AHR in mediating the toxicity of BEZO and 7,12-B[a]AQ, and found that knockdown of AHR2 rescued developmental effects caused by both compounds. Using RNA-seq and molecular docking, we identified transcriptional responses that precede developmental toxicity induced via differential interaction with AHR2. Redox-homeostasis genes were affected similarly by these OPAHs, while 7,12-B[a]AQ preferentially activated phase 1 metabolism and BEZO uniquely decreased visual system genes. Analysis of biological functions and upstream regulators suggests that BEZO is a weak AHR agonist, but interacts with other transcriptional regulators to cause developmental toxicity in an AHR-dependent manner. Furthermore, identifying ligand-dependent AHR interactions and signaling pathways is essential for understanding toxicity of this class of environmentally relevant compounds.

  6. Lethal and sublethal measures of chronic copper toxicity in the eastern narrowmouth toad, Gastrophryne carolinensis

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    LETHAL AND SUBLETHAL MEASURES OF CHRONIC COPPER TOXICITY IN THE EASTERN NARROWMOUTH TOAD, GASTROPHRYNE CAROLINENSIS R. WESLEY FLYNN,*y DAVID E. SCOTT,y WENDY KUHNE,zx DIANA SOTEROPOULOS,y and STACEY L. LANCEx ySavannah River Ecology Laboratory, University of Georgia, Aiken, South Carolina, USA zSavannah River National Laboratory, Department of Energy, University of Georgia,, Aiken, South Carolina, USA xDepartment of Biology, University of South Carolina-Aiken, Aiken, South Carolina, USA

  7. Environmental Guidance Program reference book: Toxic substances control act. Revision 7

    SciTech Connect (OSTI)

    1994-12-01

    This Reference Book contains a current copy of the Toxic Substances Control Act and those regulations that implement the statute and appear to be most relevant to DOE activities. The document is provided to DOE staff for informational purposes only and should not be interpreted as legal guidance. Questions concerning this Reference Book may be directed to Mark Petts, EH-231 (202/586-2609).

  8. Toxic Substances Control Act. Environmental Guidance Program Reference Book: Revision 6

    SciTech Connect (OSTI)

    Not Available

    1992-05-15

    This Reference Book contains a current copy of the Toxic Substances Control Act and those regulations that implement the statute and appear to be most relevant to DOE activities. The document is provided to DOE and contractor staff for informational purposes only and should not be interpreted as legal guidance. Questions concerning this Reference Book may be directed to Mark Petts, EH-231 (202/586-2609).

  9. Method for minimizing environmental release of toxic compounds in the incineration of wastes

    SciTech Connect (OSTI)

    Lerner, B.J.

    1993-08-24

    A method is described for reducing the discharge of contaminated liquid streams in the treatment of hot waste incinerator exhaust gases containing hydrochloric acid gas, particulate fly ash, toxic metal oxides and toxic organic compounds, comprising the steps of: contacting the exhaust gases with an alkaline material; reacting the major portion of the hydrochloric acid gas content of the exhaust gases with the alkaline material; removing substantially all of the reacted spent alkaline material, fly ash and other particulate matter from the gas in a solids separation stage; treating the particulate-free exhaust gases from the solids separation stage in at least two wet scrubber contact stages operating in series; operating each of the wet scrubber stages with separate dedicated salt-free aqueous scrubbing solutions; scrubbing the gas in the successive wet scrubber contact stages with acid solutions of diminishing acid concentration; absorbing in the scrubbing liquor of the wet scrubber stages substantially all of the residual hydrochloric acid and a portion of the toxic organic compounds from the particulate-free exhaust gases; operating at least the first wet scrubber stage with a recycle aqueous salt-free scrubbing solution loop; recycling a portion of the aqueous acid scrubbing solution from a downstream wet scrubber stage to the initial wet scrubber contactor stage; collecting and conveying the contaminated acid liquid blowdown stream from the initial wet scrubbing liquid recycle loop to the waste incinerator; reincinerating the acid liquor blowdown stream in the waste incinerator for destruction of the organic toxics; removing the major portion of the recycled acid gas in the first alkaline dry solids gas treatment stage and thereby eliminating discharge of a contaminated liquid stream to the environment; and thereafter recovering a purified gaseous stream from the wet scrubbing stages.

  10. Predictors of Severe Acute and Late Toxicities in Patients With Localized Head-and-Neck Cancer Treated With Radiation Therapy

    SciTech Connect (OSTI)

    Meyer, Francois; Fortin, Andre; Wang, Chang Shu; Liu, Geoffrey

    2012-03-15

    Purpose: Radiation therapy (RT) causes acute and late toxicities that affect various organs and functions. In a large cohort of patients treated with RT for localized head and neck cancer (HNC), we prospectively assessed the occurrence of RT-induced acute and late toxicities and identified characteristics that predicted these toxicities. Methods and Materials: We conducted a randomized trial among 540 patients treated with RT for localized HNC to assess whether vitamin E supplementation could improve disease outcomes. Adverse effects of RT were assessed using the Radiation Therapy Oncology Group Acute Radiation Morbidity Criteria during RT and one month after RT, and the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme at six and 12 months after RT. The most severe adverse effect among the organs/tissues was selected as an overall measure of either acute or late toxicity. Grade 3 and 4 toxicities were considered as severe. Stepwise multivariate logistic regression models were used to identify all independent predictors (p < 0.05) of acute or late toxicity and to estimate odds ratios (OR) for severe toxicity with their 95% confidence intervals (CI). Results: Grade 3 or 4 toxicity was observed in 23% and 4% of patients, respectively, for acute and late toxicity. Four independent predictors of severe acute toxicity were identified: sex (female vs. male: OR = 1.72, 95% confidence interval [CI]: 1.06-2.80), Karnofsky Performance Status (OR = 0.67 for a 10-point increment, 95% CI: 0.52-0.88), body mass index (above 25 vs. below: OR = 1.88, 95% CI: 1.22-2.90), TNM stage (Stage II vs. I: OR = 1.91, 95% CI: 1.25-2.92). Two independent predictors were found for severe late toxicity: female sex (OR = 3.96, 95% CI: 1.41-11.08) and weight loss during RT (OR = 1.26 for a 1 kg increment, 95% CI: 1.12-1.41). Conclusions: Knowledge of these predictors easily collected in a clinical setting could help

  11. Air toxics provisions of the Clean Air Act: Potential impacts on energy

    SciTech Connect (OSTI)

    Hootman, H.A.; Vernet, J.E.

    1991-11-01

    This report provides an overview of the provisions of the Clean Air Act and its Amendments of 1990 that identify hazardous air pollutant (HAP) emissions and addresses their regulation by the US Environmental Protection Agency (EPA). It defines the major energy sector sources of these HAPs that would be affected by the regulations. Attention is focused on regulations that would cover coke oven emissions; chromium emission from industrial cooling towers and the electroplating process; HAP emissions from tank vessels, asbestos-related activities, organic solvent use, and ethylene oxide sterilization; and emissions of air toxics from municipal waste combustors. The possible implications of Title III regulations for the coal, natural gas, petroleum, uranium, and electric utility industries are examined. The report discusses five major databases of HAP emissions: (1) TRI (EPA`s Toxic Release Inventory); (2) PISCES (Power Plant Integrated Systems: Chemical Emissions Studies developed by the Electric Power Research Institute); (3) 1985 Emissions Inventory on volatile organic compounds (used for the National Acid Precipitation Assessment Program); (4) Particulate Matter Species Manual (EPA); and (5) Toxics Emission Inventory (National Aeronautics and Space Administration). It also offers information on emission control technologies for municipal waste combustors.

  12. Air toxics provisions of the Clean Air Act: Potential impacts on energy

    SciTech Connect (OSTI)

    Hootman, H.A.; Vernet, J.E.

    1991-11-01

    This report provides an overview of the provisions of the Clean Air Act and its Amendments of 1990 that identify hazardous air pollutant (HAP) emissions and addresses their regulation by the US Environmental Protection Agency (EPA). It defines the major energy sector sources of these HAPs that would be affected by the regulations. Attention is focused on regulations that would cover coke oven emissions; chromium emission from industrial cooling towers and the electroplating process; HAP emissions from tank vessels, asbestos-related activities, organic solvent use, and ethylene oxide sterilization; and emissions of air toxics from municipal waste combustors. The possible implications of Title III regulations for the coal, natural gas, petroleum, uranium, and electric utility industries are examined. The report discusses five major databases of HAP emissions: (1) TRI (EPA's Toxic Release Inventory); (2) PISCES (Power Plant Integrated Systems: Chemical Emissions Studies developed by the Electric Power Research Institute); (3) 1985 Emissions Inventory on volatile organic compounds (used for the National Acid Precipitation Assessment Program); (4) Particulate Matter Species Manual (EPA); and (5) Toxics Emission Inventory (National Aeronautics and Space Administration). It also offers information on emission control technologies for municipal waste combustors.

  13. Assessment of chronic toxicity from stormwater runoff in Lincoln Creek, Milwaukee, WI

    SciTech Connect (OSTI)

    Kleist, J.; Crunkilton, R.

    1995-12-31

    Stormwater runoff is believed to be responsible for a severely degraded biotic community in Lincoln Creek, a stream which drains portions of metropolitan Milwaukee. A previous study using Ceriodaphnia dubia and Pimephales promelas indicated little or no acute toxicity could be attributed to stormwater runoff. The purpose of this study was to assess the potential for chronic toxicity in the stream during periods of stormwater runoff. Reproduction and survival in Daphnia magna, and growth and survival in P. promelas were monitored to assess chronic effects. Seven consecutive 14 day tests were performed between June and September, 1994, in eighteen flow-through aquaria housed within a US Geological Survey gauging station located adjacent to Lincoln Creek. Mortality in D. magna consistently did not occur before day 4 of exposure, but averaged 64% at day 14. Reproduction in D. magna and growth in P. promelas in surviving individuals was not significantly reduced; all effects were manifested as mortality. Results of data analysis after 14 days of exposure contrast markedly with analysis made earlier in the same test. Statistical interpretation of the mortality data at typical endpoints of 48 hours for invertebrates and 96 hours for fish failed to identify adverse impacts of stormwater runoff the authors observed in longer exposures. Short-term toxicity tests appear insensitive to the detection of contaminant related effects. Long-term tests (greater than 7 days) were needed to identify adverse biological impacts that could in part explain the severely degraded biotic community of this urban stream.

  14. A study of toxic emissions from a coal-fired gasification plant. Final report

    SciTech Connect (OSTI)

    1995-12-01

    Under the Fine Particulate Control/Air Toxics Program, the US Department of Energy (DOE) has been performing comprehensive assessments of toxic substance emissions from coal-fired electric utility units. An objective of this program is to provide information to the US Environmental Protection Agency (EPA) for use in evaluating hazardous air pollutant emissions as required by the Clean Air Act Amendments (CAAA) of 1990. The Electric Power Research Institute (EPRI) has also performed comprehensive assessments of emissions from many power plants and provided the information to the EPA. The DOE program was implemented in two. Phase 1 involved the characterization of eight utility units, with options to sample additional units in Phase 2. Radian was one of five contractors selected to perform these toxic emission assessments.Radian`s Phase 1 test site was at southern Company Service`s Plant Yates, Unit 1, which, as part of the DOE`s Clean Coal Technology Program, was demonstrating the CT-121 flue gas desulfurization technology. A commercial-scale prototype integrated gasification-combined cycle (IGCC) power plant was selected by DOE for Phase 2 testing. Funding for the Phase 2 effort was provided by DOE, with assistance from EPRI and the host site, the Louisiana Gasification Technology, Inc. (LGTI) project This document presents the results of that effort.

  15. Inhalation developmental toxicology studies: Developmental toxicity of chloroprene vapors in New Zealand white rabbits. Final report

    SciTech Connect (OSTI)

    Mast, T.J.; Evanoff, J.J.; Westerberg, R.B.; Rommereim, R.L.; Weigel, R.J.

    1994-04-01

    Chloroprene, 2-chloro-1,3-butadiene, is a colorless liquid with a pungent ethereal odor that is primarily used as an intermediate in the manufacture of neoprene rubber, and has been used as such since about 1930. This study addressed the potential for chloroprene to cause developmental toxicity in New Zealand white rabbits following gestational exposure to 0, 10, 40, or 175 ppm chloroprene vapors, 6h/dy, 7dy/wk. Each treatment group consisted of 15 artificially inseminated females exposed on 6 through 28 days of gestation (dg). Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice on 29 dg. Implants were enumerated and their status recorded and live fetuses were examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. There were no overt signs of maternal toxicity and the change in maternal body weight over the course of the study was not affected. Exposure of pregnant rabbits to chloroprene vapors on 6-28 dg had no effect on the number of implantation, the mean percent of live pups per litter, or on the incidence of resorptions per litter. The incidence of fetal malformations was not increased by exposure to chloroprene. Results of this study indicate that gestational exposure of New Zealand white rabbits to 10, 40, or 175 ppm chloroprene did not result in observable toxicity to either the dam or the offspring.

  16. Five-Year Outcomes, Cosmesis, and Toxicity With 3-Dimensional Conformal External Beam Radiation Therapy to Deliver Accelerated Partial Breast Irradiation

    SciTech Connect (OSTI)

    Rodrguez, Nria; Sanz, Xavier; Dengra, Josefa; Foro, Palmira; Membrive, Ismael; Reig, Anna; Quera, Jaume; Fernndez-Velilla, Enric; Pera, scar; Lio, Jackson; Lozano, Joan; Algara, Manuel

    2013-12-01

    Purpose: To report the interim results from a study comparing the efficacy, toxicity, and cosmesis of breast-conserving treatment with accelerated partial breast irradiation (APBI) or whole breast irradiation (WBI) using 3-dimensional conformal external beam radiation therapy (3D-CRT). Methods and Materials: 102 patients with early-stage breast cancer who underwent breast-conserving surgery were randomized to receive either WBI (n=51) or APBI (n=51). In the WBI arm, 48 Gy was delivered to the whole breast in daily fractions of 2 Gy, with or without additional 10 Gy to the tumor bed. In the APBI arm, patients received 37.5 Gy in 3.75 Gy per fraction delivered twice daily. Toxicity results were scored according to the Radiation Therapy Oncology Group Common Toxicity Criteria. Skin elasticity was measured using a dedicated device (Multi-Skin-Test-Center MC-750-B2, CKelectronic-GmbH). Cosmetic results were assessed by the physician and the patients as good/excellent, regular, or poor. Results: The median follow-up time was 5 years. No local recurrences were observed. No significant differences in survival rates were found. APBI reduced acute side effects and radiation doses to healthy tissues compared with WBI (P<.01). Late skin toxicity was no worse than grade 2 in either group, without significant differences between the 2 groups. In the ipsilateral breast, the areas that received the highest doses (ie, the boost or quadrant) showed the greatest loss of elasticity. WBI resulted in a greater loss of elasticity in the high-dose area compared with APBI (P<.05). Physician assessment showed that >75% of patients in the APBI arm had excellent or good cosmesis, and these outcomes appear to be stable over time. The percentage of patients with excellent/good cosmetic results was similar in both groups. Conclusions: APBI delivered by 3D-CRT to the tumor bed for a selected group of early-stage breast cancer patients produces 5-year results similar to those achieved with

  17. Hemithoracic Intensity Modulated Radiation Therapy After Pleurectomy/Decortication for Malignant Pleural Mesothelioma: Toxicity, Patterns of Failure, and a Matched Survival Analysis

    SciTech Connect (OSTI)

    Chance, William W.; Rice, David C.; Allen, Pamela K.; Tsao, Anne S.; Liao, Zhongxing; Chang, Joe Y.; Tang, Chad; Pan, Hubert Y.; Welsh, James W.; Mehran, Reza J.; Gomez, Daniel R.

    2015-01-01

    Purpose: To investigate safety, efficacy, and recurrence after hemithoracic intensity modulated radiation therapy after pleurectomy/decortication (PD-IMRT) and after extrapleural pneumonectomy (EPP-IMRT). Methods and Materials: In 2009-2013, 24 patients with mesothelioma underwent PD-IMRT to the involved hemithorax to a dose of 45 Gy, with an optional integrated boost; 22 also received chemotherapy. Toxicity was scored with the Common Terminology Criteria for Adverse Events v4.0. Pulmonary function was compared at baseline, after surgery, and after IMRT. Kaplan-Meier analysis was used to calculate overall survival (OS), progression-free survival (PFS), time to locoregional failure, and time to distant metastasis. Failures were in-field, marginal, or out of field. Outcomes were compared with those of 24 patients, matched for age, nodal status, performance status, and chemotherapy, who had received EPP-IMRT. Results: Median follow-up time was 12.2 months. Grade 3 toxicity rates were 8% skin and 8% pulmonary. Pulmonary function declined from baseline to after surgery (by 21% for forced vital capacity, 16% for forced expiratory volume in 1 second, and 19% for lung diffusion of carbon monoxide [P for all = .01]) and declined still further after IMRT (by 31% for forced vital capacity [P=.02], 25% for forced expiratory volume in 1 second [P=.01], and 30% for lung diffusion of carbon monoxide [P=.01]). The OS and PFS rates were 76% and 67%, respectively, at 1 year and 56% and 34% at 2 years. Median OS (28.4 vs 14.2 months, P=.04) and median PFS (16.4 vs 8.2 months, P=.01) favored PD-IMRT versus EPP-IMRT. No differences were found in grade 4-5 toxicity (0 of 24 vs 3 of 24, P=.23), median time to locoregional failure (18.7 months vs not reached, P not calculable), or median time to distant metastasis (18.8 vs 11.8 months, P=.12). Conclusions: Hemithoracic intensity modulated radiation therapy after pleurectomy/decortication produced little high-grade toxicity but

  18. The plant decapeptide OSIP108 prevents copper-induced toxicity in various models for Wilson disease

    SciTech Connect (OSTI)

    Spincemaille, Pieter; Pham, Duc-Hung; Chandhok, Gursimran; Verbeek, Jef; Zibert, Andree; Libbrecht, Louis; Schmidt, Hartmut; Esguerra, Camila V.; Witte, Peter A.M. de; Cammue, Bruno P.A.; Cassiman, David; Thevissen, Karin

    2014-10-15

    Background: Wilson disease (WD) is caused by accumulation of excess copper (Cu) due to a mutation in the gene encoding the liver Cu transporter ATP7B, and is characterized by acute liver failure or cirrhosis and neuronal cell death. We investigated the effect of OSIP108, a plant derived decapeptide that prevents Cu-induced apoptosis in yeast and human cells, on Cu-induced toxicity in various mammalian in vitro models relevant for WD and in a Cu-toxicity zebrafish larvae model applicable to WD. Methods: The effect of OSIP108 was evaluated on viability of various cell lines in the presence of excess Cu, on liver morphology of a Cu-treated zebrafish larvae strain that expresses a fluorescent reporter in hepatocytes, and on oxidative stress levels in wild type AB zebrafish larvae. Results: OSIP108 increased not only viability of Cu-treated CHO cells transgenically expressing ATP7B and the common WD-causing mutant ATP7B{sup H1069Q}, but also viability of Cu-treated human glioblastoma U87 cells. Aberrancies in liver morphology of Cu-treated zebrafish larvae were observed, which were further confirmed as Cu-induced hepatotoxicity by liver histology. Injections of OSIP108 into Cu-treated zebrafish larvae significantly increased the amount of larvae with normal liver morphology and decreased Cu-induced production of reactive oxygen species. Conclusions: OSIP108 prevents Cu-induced toxicity in in vitro models and in a Cu-toxicity zebrafish larvae model applicable to WD. General significance: All the above data indicate the potential of OSIP108 as a drug lead for further development as a novel WD treatment. - Highlights: • Wilson disease (WD) is characterized by accumulation of toxic copper (Cu). • OSIP108 increases viability of Cu-treated cellular models applicable to WD. • OSIP108 injections preserve liver morphology of Cu-treated zebrafish larvae. • OSIP108 injections into zebrafish larvae abrogates Cu-induced oxidative stress.

  19. Nanoscale copper in the soil–plant system – toxicity and underlying potential mechanisms

    SciTech Connect (OSTI)

    Anjum, Naser A.; Adam, Vojtech; Iqbal, Muhammad; Lukatkin, Alexander S.; Ahmad, Iqbal

    2015-04-15

    Nanoscale copper particles (nano-Cu) are used in many antimicrobial formulations and products for their antimicrobial activity. They may enter deliberately and/or accidentally into terrestrial environments including soils. Being the major ‘eco-receptors’ of nanoscale particles in the terrestrial ecosystem, soil–microbiota and plants (the soil–plant system) have been used as a model to dissect the potential impact of these particles on the environmental and human health. In the soil–plant system, the plant can be an indirect non-target organism of the soil-associated nano-Cu that may in turn affect plant-based products and their consumers. By all accounts, information pertaining to nano-Cu toxicity and the underlying potential mechanisms in the soil–plant system remains scanty, deficient and little discussed. Therefore, based on some recent reports from (bio)chemical, molecular and genetic studies of nano-Cu versus soil–plant system, this article: (i) overviews the status, chemistry and toxicity of nano-Cu in soil and plants, (ii) discusses critically the poorly understood potential mechanisms of nano-Cu toxicity and tolerance both in soil–microbiota and plants, and (iii) proposes future research directions. It appears from studies hitherto made that the uncontrolled generation and inefficient metabolism of reactive oxygen species through different reactions are the major factors underpinning the overall nano-Cu consequences in both the systems. However, it is not clear whether the nano-Cu or the ion released from it is the cause of the toxicity. We advocate to intensify the multi-approach studies focused at a complete characterization of the nano-Cu, its toxicity (during life cycles of the least-explored soil–microbiota and plants), and behavior in an environmentally relevant terrestrial exposure setting. Such studies may help to obtain a deeper insight into nano-Cu actions and address adequately the nano-Cu-associated safety concerns in the

  20. Quality of Life and Toxicity From Passively Scattered and Spot-Scanning Proton Beam Therapy for Localized Prostate Cancer

    SciTech Connect (OSTI)

    Pugh, Thomas J. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Munsell, Mark F. [Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Choi, Seungtaek; Nguyen, Quyhn Nhu; Mathai, Benson [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Zhu, X. Ron; Sahoo, Narayan; Gillin, Michael; Johnson, Jennifer L.; Amos, Richard A. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Dong, Lei [Scripps Proton Therapy Center, San Diego, California (United States); Mahmood, Usama; Kuban, Deborah A.; Frank, Steven J.; Hoffman, Karen E.; McGuire, Sean E. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lee, Andrew K., E-mail: aklee@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-12-01

    Purpose: To report quality of life (QOL)/toxicity in men treated with proton beam therapy for localized prostate cancer and to compare outcomes between passively scattered proton therapy (PSPT) and spot-scanning proton therapy (SSPT). Methods and Materials: Men with localized prostate cancer enrolled on a prospective QOL protocol with a minimum of 2 years' follow-up were reviewed. Comparative groups were defined by technique (PSPT vs SSPT). Patients completed Expanded Prostate Cancer Index Composite questionnaires at baseline and every 3-6 months after proton beam therapy. Clinically meaningful differences in QOL were defined as ?0.5 baseline standard deviation. The cumulative incidence of modified Radiation Therapy Oncology Group grade ?2 gastrointestinal (GI) or genitourinary (GU) toxicity and argon plasma coagulation were determined by the Kaplan-Meier method. Results: A total of 226 men received PSPT, and 65 received SSPT. Both PSPT and SSPT resulted in statistically significant changes in sexual, urinary, and bowel Expanded Prostate Cancer Index Composite summary scores. Only bowel summary, function, and bother resulted in clinically meaningful decrements beyond treatment completion. The decrement in bowel QOL persisted through 24-month follow-up. Cumulative grade ?2 GU and GI toxicity at 24 months were 13.4% and 9.6%, respectively. There was 1 grade 3 GI toxicity (PSPT group) and no other grade ?3 GI or GU toxicity. Argon plasma coagulation application was infrequent (PSPT 4.4% vs SSPT 1.5%; P=.21). No statistically significant differences were appreciated between PSPT and SSPT regarding toxicity or QOL. Conclusion: Both PSPT and SSPT confer low rates of grade ?2 GI or GU toxicity, with preservation of meaningful sexual and urinary QOL at 24 months. A modest, yet clinically meaningful, decrement in bowel QOL was seen throughout follow-up. No toxicity or QOL differences between PSPT and SSPT were identified. Long-term comparative results in a larger patient

  1. WE-D-BRE-03: Late Toxicity Following Photon Or Proton Radiotherapy in Patients with Brain Tumors

    SciTech Connect (OSTI)

    Munbodh, R; Ding, X; Yin, L; Anamalayil, S; Dorsey, J; Lustig, R; Alonso-Basanta, M

    2014-06-15

    Purpose: To identify indicators of Late Grade 3 (LG3) toxicity, late vision and hearing changes in patients treated for primary brain tumors with photon (XRT) or proton radiotherapy (PRT). Methods: We retrospectively reviewed 102 patients who received brain XRT or PRT to doses of 54 or 59.6 Gy in daily fractions of 1.8–2 Gy. Of the 80 patients (34 XRT, 39 PRT and 7 both modalities) reviewed for indicators of LG3 toxicity, 25 developed LG3 toxicity 90 to 500 days after radiotherapy completion. 55 patients had less than LG3 toxicity > 500 days after treatment. In that time, late vision and hearing changes were seen in 44 of 75 and 25 of 78 patients, respectively. The correlation between late toxicity and prescription dose, planning target volume (PTV) size, and doses to the brainstem, brain, optic chiasm, optic nerves, eyes and cochlea was evaluated. A two-tailed Fisher's exact test and Wilcoxon rank sum test were used for the statistical analysis for XRT, PRT and all patients combined. Results: Exceeding the 54 Gy-5% dose-volume brainstem constraint, but not the optic structure constraints, was significantly correlated (p < 0.05) with late vision changes in all three groups. Exceeding maximum and mean cochlear doses of 45 and 30 Gy, respectively, was a significant indicator of hearing changes (p < 0.05) in PRT patients and all patients combined. In a sub-group of 52 patients in whom the brain was contoured, the absolute brain volume receiving ≤ 50 Gy and > 60 Gy was significantly larger in patients with LG3 toxicity for all patients combined (p < 0.05). Prescription dose, brainstem dose and PTV volume were not correlated to LG3 toxicity. Conclusion: Our results indicate the importance of minimizing the brain volume irradiated, and brainstem and cochlea doses to reduce the risk of late toxicities following brain radiotherapy.

  2. Toxic effect of mercury on salmon larval, Oncorhynchus keta and O. kisutch

    SciTech Connect (OSTI)

    Petukhov, S.A.; Storozhuk, N.G.

    1980-01-01

    Chum salmon and coho salmon eggs were obtained at the stage of commencement of organogenesis. Following acclimation for 2 days, eggs were placed in batches of 500 on frames and incubated in 1 l of water at a constant 8/sup 0/C. Coho eggs were incubated in mercuric chloride solutions for 25 days. An experiment with larvae lasted 140 days. Chum embryos were placed in the same mercuric chloride solutions after hatching and were used in the experiment for 90 days. Mortality of the chum occurred during the first 40 days of exposure; it was 15% in the variant in which the concentration of the toxicant was 1 micro g/l, 13% at 5 micro g/l and 30% at 25 micro g/l, 12% in the control. Mass mortality of coho larvae was noted from beginning to end of hatching and was 12% in the variants in which the concentration of the toxicant was 1 micro g/l, 11% at 5 and 25 micro g/l, and 3% in the control. Consequently, the coho was more tolerant of mercury. An appreciable percentage mortality of larvae of this species was noted at mercury concentrations of 25 micro g/l. It is suggested that when fish develop from the stage of embryogenesis under conditions of an increased content of toxicants of the heavy metal group the most resistant individuals survive. A reduction in the concentration of biologically active metals was noted in salmon larvae reared in an environment with an increased concentration of mercury. 9 references, 1 figure, 3 tables.

  3. Metal toxicity evaluation of Savannah River Plant saltstone comparison of EP and TCLP test results

    SciTech Connect (OSTI)

    Langton, C A

    1988-01-01

    Saltstone is the waste treatment and disposal concept for low-level defense waste at the Savannah River Plant. The waste is a sodium salt solution which has about 230 ..mu..CiL in addition to the hazardous characteristics of corrosivity and metal toxicity (Cr/sup +6/ > 100 ppM). Two EPA test procedures are routinely used at SRP to evaluate metal toxicity of wastes and wasteforms. 1) the Extraction Procedure (EP); and 2) the Toxicity Characterization Leaching Procedure (TCLP). The EP test is required by SCDHEC and EPA. The TCLP is used to evaluate the effect of increased surface area on metal leaching from the various SRP wasteforms. EP and TCLP test results are presented for two types of wasteforms, a cement-based saltstone and for a slag-based saltstone. The slag saltstone chemically stabilizes and also physically entraps the chromium. For waste solutions with low to intermediate metal concentrations (up to 5000 ppM), the TCLP extracts typically have lower metal values than the EP extracts. This is attributed to the faster neutralization of the acetic acid by the crushed TCLP sample. Crushing increases surface area and consequently releases more alkalinity from the wasteform matrix and the wasteform pore solution. Metal concentrations in the EP and TCLP extracts are proportional to the concentrations of metals in the pore solution for both the cement or slag-based wasteforms. The pore solution concentrations for cement wasteforms are directly related to the soluble metal concentration in the waste. The metal concentration in the slag wasteform pore solutions are significantly lower than the waste because these metals are reduced lower valences and precipitated as insoluble solid phases. 3 refs., 3 figs., 5 tabs.

  4. Acute and chronic toxicity of uranium compounds to Ceriodaphnia-Daphnia dubia

    SciTech Connect (OSTI)

    Pickett, J.B.; Specht, W.L.; Keyes, J.L.

    1993-03-31

    A study to determine the acute and chronic toxicity of uranyl nitrate, hydrogen uranyl phosphate, and uranium dioxide to the organism Ceriodaphnia dubia was conducted. The toxicity tests were conducted by two independent environmental consulting laboratories. Part of the emphasis for this determination was based on concerns expressed by SCDHEC, which was concerned that a safety factor of 100 must be applied to the previous 1986 acute toxicity result of 0.22 mg/L for Daphnia pulex, This would have resulted in the LETF release limits being based on an instream concentration of 0.0022 mg/L uranium. The NPDES Permit renewal application to SCDHEC utilized the results of this study and recommended that the LETF release limit for uranium be based an instream concentration of 0.004 mg/L uranium. This is based on the fact that the uranium releases from the M-Area LETF will be in the hydrogen uranyl phosphate form, or a uranyl phosphate complex at the pH (6--10) of the Liquid Effluent Treatment Facility effluent stream, and at the pH of the receiving stream (5.5 to 7.0). Based on the chronic toxicity of hydrogen uranyl phosphate, a lower uranium concentration limit for the Liquid Effluent Treatment Facility outfall vs. the existing NPDES permit was recommended: The current NPDES permit ``Guideline`` for uranium at outfall M-004 is 0.500 mg/L average and 1.0 mg/L maximum, at a design flowrate of 60 gpm. It was recommended that the uranium concentration at the M-004 outfall be reduced to 0.28 mg/L average, and 0.56 mg/L, maximum, and to reduce the design flowrate to 30 gpm. The 0.28 mg/L concentration will provide an instream concentration of 0.004 mg/L uranium. The 0.28 mg/L concentration at M-004 is based on the combined flows from A-014, A-015, and A-011 outfalls (since 1985) of 1840 gpm (2.65 MGD) and was the flow rate which was utilized in the 1988 NPDES permit renewal application.

  5. Migration and Retardation of Chemical Toxic Components from Radioactive Waste - Hydrochemical Aspects

    SciTech Connect (OSTI)

    Jedinakova-Krizova, V.; Hanslik, E.

    2003-02-24

    A systematic analysis of nuclear power plant (NPP) operation and radioactive wastes disposal (near-surface disposal and geologic disposal) in underground repositories has provided the basis for a comparison between the radiotoxicity and chemotoxicity as part of an EIA (environmental impact assessment) procedure. This contribution summarizes the hydrochemical mechanisms of transport and retardation processes, chemistry and migration behavior of radionuclides and chemical toxics in natural sorbents, especially bentonites. The effect of solubility and dissolution reactions, diffusion and sorption/desorption, complexation and variations in the aqueous phase composition, pH-value and oxidation-reduction properties and other phenomena affecting distribution coefficients (Kd values) is discussed.

  6. An empirical analysis of exposure-based regulation to abate toxic air pollution

    SciTech Connect (OSTI)

    Marakovits, D.M.; Considine, T.J.

    1996-11-01

    Title III of the 1990 Clean Air Act Amendments requires the Environmental Protection Agency to regulate 189 air toxics, including emissions from by-product coke ovens. Economists criticize the inefficiency of uniform standards, but Title III makes no provision for flexible regulatory instruments. Environmental health scientists suggest that population exposure, not necessarily ambient air quality, should motivate environmental air pollution policies. Using an engineering-economic model of the United States steel industry, we estimate that an exposure-based policy can achieve the same level of public health as coke oven emissions standards and can reduce compliance costs by up to 60.0%. 18 refs., 3 figs., 1 tab.

  7. Reduction of U(VI) and Toxic Metals by Desulfovibrio Cytochrome c3

    SciTech Connect (OSTI)

    Wall, Judy D.

    2003-06-01

    The project, ''Reduction of U(VI) and toxic metals by Desulfovibrio cytochrome c3'', is designed to obtain spectroscopic information for or against a functional interaction of cytochrome c3 and uranium in the whole cells. That is, is the cytochrome c3 the uranium reductase? Our approach has been to start with purified cytochrome and determine any unique spectral disturbances during electron flow to U(VI). Then we will attempt to identify these signals emanating from cells actively reducing uranium. This project is being carried out in collaboration with Dr. William Woodruff at the Los Alamos National Laboratory where the spectral experiments are being carried out.

  8. Polychlorinated biphenyls (PCBs): Toxicity and metabolism. (Latest citations from Pollution abstracts). Published Search

    SciTech Connect (OSTI)

    1996-02-01

    The bibliography contains citations concerning the toxicity and metabolism of polychlorinated biphenyl compounds (PCBs). The effects of PCB exposure on the environment, workplace, and human health are examined. The mechanisms of uptake and metabolism for both humans and animals are discussed. Clinical aspects of exposure are examined, including poisoning, liver disease, carcinogenesis, neurological disorders, and reproductive effects. PCBs as pollutants and their environmental fate are covered in related published bibliographies. (Contains 50-250 citations and includes a subject term index and title list.) (Copyright NERAC, Inc. 1995)

  9. Polychlorinated biphenyls (PCBs): Toxicity and metabolism. (Latest citations from Pollution abstracts). Published Search

    SciTech Connect (OSTI)

    1995-02-01

    The bibliography contains citations concerning the toxicity and metabolism of polychlorinated biphenyl compounds (PCBs). The effects of PCB exposure on the environment, workplace, and human health are examined. The mechanisms of uptake and metabolism for both humans and animals are discussed. Clinical aspects of exposure are examined, including poisoning, liver disease, carcinogenesis, neurological disorders, and reproductive effects. PCBs as pollutants and their environmental fate are covered in related published bibliographies. (Contains a minimum of 187 citations and includes a subject term index and title list.)

  10. Polychlorinated biphenyls (PCBs): Toxicity and metabolism. (Latest citations from Pollution Abstracts). Published Search

    SciTech Connect (OSTI)

    1997-05-01

    The bibliography contains citations concerning the toxicity and metabolism of polychlorinated biphenyl compounds (PCBs). The effects of PCB exposure on the environment, workplace, and human health are examined. The mechanisms of uptake and metabolism for both humans and animals are discussed. Clinical aspects of exposure are examined, including poisoning, liver disease, carcinogenesis, neurological disorders, and reproductive effects. PCBs as pollutants and their environmental fate are covered in related published bibliographies. (Contains 50-250 citations and includes a subject term index and title list.) (Copyright NERAC, Inc. 1995)

  11. Acute environmental toxicity and persistence of methyl salicylate: A chemical agent simulant. Final report

    SciTech Connect (OSTI)

    Cataldo, D.A.; Ligotke, M.W.; Harvey, S.D.; Fellows, R.J.; Li, S.W.

    1994-06-01

    The interactions of methyl salicylate with plant foliage and soils were assessed using aerosol/vapor exposure methods. Measurements of deposition velocity and residence times for soils and foliar surfaces are reported. Severe plant contact toxicity was observed at foliar mass-loading levels above 4 {mu}g/cm{sup 2} leaf; however, recovery was noted after four to fourteen days. Methyl salicylate has a short-term effect on soil dehydrogenase activity, but not phosphatase activity. Results of the earthworm bioassay indicated only minimal effects on survival.

  12. Control of Toxic Chemicals in Puget Sound, Phase 3: Study of Atmospheric Deposition of Air Toxics to the Surface of Puget Sound

    SciTech Connect (OSTI)

    Brandenberger, Jill M.; Louchouarn, Patrick; Kuo, Li-Jung; Crecelius, Eric A.; Cullinan, Valerie I.; Gill, Gary A.; Garland, Charity R.; Williamson, J. B.; Dhammapala, R.

    2010-07-05

    The results of the Phase 1 Toxics Loading study suggested that runoff from the land surface and atmospheric deposition directly to marine waters have resulted in considerable loads of contaminants to Puget Sound (Hart Crowser et al. 2007). The limited data available for atmospheric deposition fluxes throughout Puget Sound was recognized as a significant data gap. Therefore, this study provided more recent or first reported atmospheric deposition fluxes of PAHs, PBDEs, and select trace elements for Puget Sound. Samples representing bulk atmospheric deposition were collected during 2008 and 2009 at seven stations around Puget Sound spanning from Padilla Bay south to Nisqually River including Hood Canal and the Straits of Juan de Fuca. Revised annual loading estimates for atmospheric deposition to the waters of Puget Sound were calculated for each of the toxics and demonstrated an overall decrease in the atmospheric loading estimates except for polybrominated diphenyl ethers (PBDEs) and total mercury (THg). The median atmospheric deposition flux of total PBDE (7.0 ng/m2/d) was higher than that of the Hart Crowser (2007) Phase 1 estimate (2.0 ng/m2/d). The THg was not significantly different from the original estimates. The median atmospheric deposition flux for pyrogenic PAHs (34.2 ng/m2/d; without TCB) shows a relatively narrow range across all stations (interquartile range: 21.2- 61.1 ng/m2/d) and shows no influence of season. The highest median fluxes for all parameters were measured at the industrial location in Tacoma and the lowest were recorded at the rural sites in Hood Canal and Sequim Bay. Finally, a semi-quantitative apportionment study permitted a first-order characterization of source inputs to the atmosphere of the Puget Sound. Both biomarker ratios and a principal component analysis confirmed regional data from the Puget Sound and Straits of Georgia region and pointed to the predominance of biomass and fossil fuel (mostly liquid petroleum products such

  13. Determination of the toxicity characteristic for metals in soil: A comparison of the toxicity characteristic leaching procedure and total metal determination

    SciTech Connect (OSTI)

    Bass, D.A.; Taylor, J.D.

    1994-12-01

    A comparison is made of the concentrations of metals extracted from soils using the Toxicity Characteristic Leaching Procedure (TCLP) and a total determination method. This information is of interest in two ways. First, it is hoped that a relationship might be established between the amount of each metal determined after extraction by the TCLP and the amount determined using a total determination method. And second, data are also presented which indicate the general extractability of various metals in soil samples using the TCLP. This study looks specifically at inorganic elements (Sb, As, Ba, Cd, Cu, Cr, Pb, Mg, Hg, Se, Ag, Sn, and Zn) in soils from a firing range. Results show that total determination methods for metals can not generally be used for heterogeneous samples, such as soil samples from a firing range. Some correlation between a total determination method and TCLP was observed when Ba and Cd were present in the samples at lower concentrations (less than 80 mg/kg for Ba and less than 25 mg/kg for Cd); however, additional data are necessary to verify this correlation.

  14. Comparative toxicity of pentachlorophenol to three earthworm species in artificial soil

    SciTech Connect (OSTI)

    Fitzgerald, D.; Lanno, R.P.; Farwell, A.; Dixon, D.G.

    1994-12-31

    Although methods for standardized toxicity tests with earthworms exist, many of the test parameters and conditions have not been validated in actual tests and with different species of worms. This study evaluated the toxicity of pentachlorophenol (PCP) to three species of earthworms, Lumbricus terrestris, Eisenia fetida, and Eudrilus eugeniae using various methods of data analysis and body residues. Tests were conducted in artificial soil for a period of 28 days or until an Acute Lethality Threshold (ALT) was reached. An intensive temporal sampling regime was applied to generate sufficient data for the accurate estimation of ALTs using both LC50/time and time-to-death/soil concentration methods of data analysis. L. terrestris was tested at 15 C, E. eugeniae at 24 C, and E. fetida at both temperatures. Total body residues of PCP were measured by GC following cryogenic separation of the lipid fraction of the worm. ALTs were significantly different between E. fetida and the two larger species of worms. No effect of temperature on the ALT for E. fetida was observed, although the time taken to reach the ALT increased at the lower temperature. The relationship of PCP residues at mortality will be discussed in terms of the effects of species, body size and temperature. Limitations of the artificial soil based upon growth curves of worms will also be examined.

  15. Structure-toxicity assessment of metabolites of the aerobic bacterial transformation of substituted naphthalenes

    SciTech Connect (OSTI)

    LeBlond, J.D.; Applegate, B.M.; Menn, F.M.; Schultz, T.W.; Sayler, G.S.

    2000-05-01

    Pseudomonas fluorescens 5R, a naphthalene-degrading bacterium isolated from manufactured gas plant soil contaminated with polycyclic aromatic hydrocarbons, was examined for its degradative capacity of a number of substituted naphthalenes. In general, those compounds substituted on only one ring with an electrically neutral substituent were found to be transformed primarily to substituted salicylic acids according to the classical (NAH7) naphthalene dioxygenase-initiated upper pathway reactions of the naphthalene degradative pathway (i.e., the NAH system). Dimethylnaphthalenes with a substituent on each ring, and certain halogenated naphthalenes, were transformed via a monohydroxylation reaction to form hydroxylated dead-end products. Of the substituted salicylic acids examined, only 3- and 4-methylsalicylic acid, the respective products of the degradation of 1- and 2-methylnaphthalene, were further degraded by salicylate hydroxylase and catechol 2,3-dioxygenase, the first two enzymes of the NAH lower pathway. Using the Tetrahymena pyriformis acute toxicity assay, many of the monohydroxylated products of incomplete biodegradation were found to be polar narcotics. Substituted salicylic acids that are not further degraded by the NAH lower pathway were found to be toxic via carboxylic acid narcosis.

  16. ABB`s investigations into air toxic emissions from fossil fuel and MSW combustion

    SciTech Connect (OSTI)

    Wesnor, J.D.

    1994-12-31

    Since passage of the Clean Air Act, Asea Brown Boveri (ABB) has been actively developing a knowledge base on the Title 3 hazardous air pollutants, more commonly called air toxics. As ABB is a multinational company, US operating companies are able to call upon work performed by European counterparts, who have faced similar legislation several years ago. In addition to the design experience and database acquired in Europe, ABB Inc. has been pursuing several other avenues to expand its air toxics knowledge. ABB Combustion Engineering (ABB CE) is presently studying the formation of organic pollutants within the combustion furnace and partitioning of trace metals among the furnace outlet streams. ABB Environmental Systems (ABBES) has reviewed available and near-term control technologies and methods. Also, both ABB CE and ABBES have conducted source sampling and analysis at commercial installations for hazardous air pollutants to determine the emission rates and removal performance of various types of equipment. Several different plants hosted these activities, allowing for variation in fuel type and composition, boiler configuration, and air pollution control equipment. This paper discusses the results of these investigations.

  17. Chronomodulation of topotecan or X-radiation treatment increases treatment efficacy without enhancing acute toxicity

    SciTech Connect (OSTI)

    Mullins, Dana; Proulx, Denise; Saoudi, A.; Ng, Cheng E. . E-mail: cng@ohri.ca

    2005-05-01

    Purpose: Topotecan (TPT), a camptothecin analog, is currently used to treat human ovarian and small-cell lung cancer and is in clinical trials for other tumor sites. However, it is unknown whether chronomodulation of TPT treatment is beneficial. We examined the effects of administering TPT or X-radiation (XR) alone at different times of the day or night. Methods: We treated mice bearing human colorectal tumor xenografts at four different times representing the early rest period (9 AM or 3 HALO [hours after light onset]), late rest period (3 PM or 9 HALO), early active period (9 PM or 15 HALO), and late active period (3 AM or 21 HALO) of the mice. We gave either TPT (12 mg/kg, injected i.p.) or XR (4 Gy, directed to the tumor) twice weekly on Days 0, 4, 7, 10 within 2 weeks. Results: Treatment with either TPT or XR at 3 AM demonstrated the greatest efficacy (measured by a tumor regrowth assay) without significantly increasing acute toxicity (assessed by a decrease in leukocyte counts or body weight). Conversely, treatment at 3 PM, in particular, showed increased toxicity without any enhanced efficacy. Conclusions: Our study provided the first evidence that chronomodulation of TPT treatments, consistent with the findings of other camptothecin analogs, is potentially clinically beneficial. Additionally, our findings suggest that chronomodulation of fractionated XR treatments is also potentially clinically beneficial.

  18. Hyperfractionated Accelerated Radiotherapy (HART) for Anaplastic Thyroid Carcinoma: Toxicity and Survival Analysis

    SciTech Connect (OSTI)

    Dandekar, Prasad; Rhys-Evans, Peter; Harrington, Kevin; Nutting, Christopher; Newbold, Kate

    2009-06-01

    Purpose: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive cancers, and the current protocol of hyperfractionated accelerated radiotherapy was initiated to improve survival while limiting toxicities. Methods and Materials: All patients with ATC from 1991 to 2002 were accrued and received megavoltage radiotherapy from the mastoid processes to the carina up to 60 Gy in twice-daily fractions of 1.8 and 2 Gy, 6 hours apart. Results: Thirty-one patients were accrued with a median age of 69 years, and 55% were women. Debulking was performed in 26%, and total thyroidectomy, in 6%, whereas 68% received radical radiotherapy alone. Local control data were available for 27 patients: 22% had a complete response, 26% had a partial response, 15% showed progressive disease, and 37% showed static disease. Median overall survival for all 31 patients was 70 days (95% confidence interval, 40-99). There was no significant difference in median survival between patients younger (70 days) and older than 70 years (42 days), between men (70 days) and women (49days), and between patients receiving postoperative radiotherapy (77 days) and radical radiotherapy alone (35 days). Grade III or higher skin erythema was seen in 56% patients; desquamation in 21%; dysphagia in 74%; and esophagitis in 79%. Conclusion: The current protocol failed to offer a significant survival benefit, was associated with severe toxicities, and thus was discontinued. There is a suggestion that younger patients with operable disease have longer survival, but this would require a larger study to confirm it.

  19. Toxicity of Select Organic Acids to the Slightly Thermophilic Acidophile Acidithiobaccillus Caldus

    SciTech Connect (OSTI)

    John E Aston; William A Apel; Brady D Lee; Brent M Peyton

    2009-02-01

    Acidithiobacillus caldus is a thermophilic acidophile found in commercial biomining, acid mine drainage systems, and natural environments. Previous work has characterized A. caldus as a chemolithotrophic autotroph capable of utilizing reduced sulfur compounds under aerobic conditions. Organic acids are especially toxic to chemolithotrophs in low-pH environments, where they diffuse more readily into the cell and deprotonate within the cytoplasm. In the present study, the toxic effects of oxaloacetate, pyruvate, 2-ketoglutarate, acetate, malate, succinate, and fumarate on A. caldus strain BC13 were examined under batch conditions. All tested organic acids exhibited some inhibitory effect. Oxaloacetate was observed to inhibit growth completely at a concentration of 250 M, whereas other organic acids were completely inhibitory at concentrations of between 1,000 and 5,000 M. In these experiments, the measured concentrations of organic acids decreased with time, indicating uptake or assimilation by the cells. Phospholipid fatty acid analyses indicated an effect of organic acids on the cellular envelope. Notable differences included an increase in cyclic fatty acids in the presence of organic acids, indicating possible instability of the cellular envelope. This was supported by field emission scanning-electron micrographs showing blebbing and sluffing in cells grown in the presence of organic acids.

  20. Structure of the toxic core of α-synuclein from invisible crystals

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Rodriguez, Jose A.; Ivanova, Magdalena I.; Sawaya, Michael R.; Cascio, Duilio; Reyes, Francis E.; Shi, Dan; Sangwan, Smriti; Guenther, Elizabeth L.; Johnson, Lisa M.; Zhang, Meng; et al

    2015-09-09

    We report that the protein α-synuclein is the main component of Lewy bodies, the neuron-associated aggregates seen in Parkinson disease and other neurodegenerative pathologies. An 11-residue segment, which we term NACore, appears to be responsible for amyloid formation and cytotoxicity of human α-synuclein. Here we describe crystals of NACore that have dimensions smaller than the wavelength of visible light and thus are invisible by optical microscopy. As the crystals are thousands of times too small for structure determination by synchrotron X-ray diffraction, we use micro-electron diffraction to determine the structure at atomic resolution. The 1.4 Å resolution structure demonstrates thatmore » this method can determine previously unknown protein structures and here yields, to our knowledge, the highest resolution achieved by any cryo-electron microscopy method to date. The structure exhibits protofibrils built of pairs of face-to-face β-sheets. X-ray fibre diffraction patterns show the similarity of NACore to toxic fibrils of full-length α-synuclein. Finally, the NACore structure, together with that of a second segment, inspires a model for most of the ordered portion of the toxic, full-length α-synuclein fibril, presenting opportunities for the design of inhibitors of α-synuclein fibrils.« less

  1. Small heat shock proteins protect against {alpha}-synuclein-induced toxicity and aggregation

    SciTech Connect (OSTI)

    Outeiro, Tiago Fleming [Alzheimer's Research Unit, MassGeneral Institute for Neurodegenerative Disease, MGH, Harvard Medical School, CNY 114, 16th Street, Charlestown, MA 02129 (United States); Klucken, Jochen [Alzheimer's Research Unit, MassGeneral Institute for Neurodegenerative Disease, MGH, Harvard Medical School, CNY 114, 16th Street, Charlestown, MA 02129 (United States); Strathearn, Katherine E. [Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907-2091 (United States); Liu Fang [Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907-2091 (United States); Nguyen, Paul [Alzheimer's Research Unit, MassGeneral Institute for Neurodegenerative Disease, MGH, Harvard Medical School, CNY 114, 16th Street, Charlestown, MA 02129 (United States); Rochet, Jean-Christophe [Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907-2091 (United States); Hyman, Bradley T. [Alzheimer's Research Unit, MassGeneral Institute for Neurodegenerative Disease, MGH, Harvard Medical School, CNY 114, 16th Street, Charlestown, MA 02129 (United States); McLean, Pamela J. [Alzheimer's Research Unit, MassGeneral Institute for Neurodegenerative Disease, MGH, Harvard Medical School, CNY 114, 16th Street, Charlestown, MA 02129 (United States)]. E-mail: touteiro@partners.org

    2006-12-22

    Protein misfolding and inclusion formation are common events in neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD) or Huntington's disease (HD). {alpha}-Synuclein (aSyn) is the main protein component of inclusions called Lewy bodies (LB) which are pathognomic of PD, Dementia with Lewy bodies (DLB), and other diseases collectively known as LB diseases. Heat shock proteins (HSPs) are one class of the cellular quality control system that mediate protein folding, remodeling, and even disaggregation. Here, we investigated the role of the small heat shock proteins Hsp27 and {alpha}B-crystallin, in LB diseases. We demonstrate, via quantitative PCR, that Hsp27 messenger RNA levels are {approx}2-3-fold higher in DLB cases compared to control. We also show a corresponding increase in Hsp27 protein levels. Furthermore, we found that Hsp27 reduces aSyn-induced toxicity by {approx}80% in a culture model while {alpha}B-crystallin reduces toxicity by {approx}20%. In addition, intracellular inclusions were immunopositive for endogenous Hsp27, and overexpression of this protein reduced aSyn aggregation in a cell culture model.

  2. Evaluation of 2,3,7,8 specific congener and toxic potency of persistent polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans in cetaceans from the Mediterranean Sea, Italy

    SciTech Connect (OSTI)

    Jimenez, B.; Gonzalez, M.J.; Jimenez, O.; Reich, S.; Eljarrat, E.; Rivera, J.

    2000-03-01

    The present study investigates individual 2,3,7,8-substituted polychlorinated dibenzo-p-dioxin (PCDD) and polychlorinated dibenzofuran (PCDF) concentrations in cetaceans and assesses the PCDD and PCDF contributions to the total TCDD equivalent concentration. Liver samples of a variety of cetaceans species found stranded along the Italian coasts during the period of 1987--1992 were analyzed for PCDDs and PCDFs. The main aims were to scrutinize levels and patterns of PCDDs and PCDFs for the first time in cetaceans from the Mediterranean Sea and to estimate whether chlorinated compounds mentioned are implicated in the exceptionally high mortality of dolphins that occurred in the Mediterranean sea during 1990--1992. PCDD and PCDF profiles were dominated by congeners OCCD and OCDF. The new toxic equivalency factors recommended by WHO in 1997 were used for calculation of dioxin-like toxicity. On the basis of their previous study of PCBs, the overall TEQ calculated from the 2,3,7,8-substituted PCDDs and PCDFs do not contribute as much dioxin-like toxicity as PCBs.

  3. Toxicity of polychlorinated diphenyl ethers in hydra attenuata and in rat whole-embryo culture. Master's thesis

    SciTech Connect (OSTI)

    Becker, M.C.

    1991-05-01

    Polychlorinated diphenyl ethers (PCDEs) are a class of biaryl compounds that have little commercial application, but appear to be widespread in the environment. They have been found in wood preservative waste dumpsites and in fly ash from municipal waste incinerators. They have been detected in bird eggs and tissues, fish, and other edible marine organisms in the United States, Canada, and Europe. There are limited reports in the extant literature on the toxicity of PCDEs. This study was designed to evaluate the toxicity of selected PCDEs in cultures of Hydra attenuata and post-implantation rat whole embryos. The toxicity of several closely related polychlorinated biphenyls (PCBs) was evaluated in both cultures and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was evaluated in whole embryo culture. Embryonic growth and development parameters (yolk sac diameter, crown-rump length, somite count, and DNA and protein content) and gross morphology were determined. Findings indicated that these chemicals were neither embryotoxic nor teratogenic. Thus, the PCDEs, which elicit other diverse toxic and biochemical responses in rodents, are relatively inactive in these bioassays for developmental toxicity.

  4. Comparative hazard analysis and toxicological modeling of diverse nanomaterials using the embryonic zebrafish (EZ) metric of toxicity

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Harper, Bryan; Thomas, Dennis G.; Chikkagoudar, Satish; Baker, Nathan A.; Tang, Kaizhi; Heredia-Langner, Alejandro; Lins, Roberto D.; Harper, Stacey

    2015-06-04

    The integration of rapid assays, large data sets, informatics and modeling can overcome current barriers in understanding nanomaterial structure-toxicity relationships by providing a weight-of-the-evidence mechanism to generate hazard rankings for nanomaterials. Here we present the use of a rapid, low-cost assay to perform screening-level toxicity evaluations of nanomaterials in vivo. Calculated EZ Metric scores, a combined measure of morbidity and mortality, were established at realistic exposure levels and used to develop a predictive model of nanomaterial toxicity. Hazard ranking and clustering analysis of 68 diverse nanomaterials revealed distinct patterns of toxicity related to both core composition and outermost surface chemistrymore » of nanomaterials. The resulting clusters guided the development of a predictive model of gold nanoparticle toxicity to embryonic zebrafish. In addition, our findings suggest that risk assessments based on the size and core composition of nanomaterials alone may be wholly inappropriate, especially when considering complex engineered nanomaterials. These findings reveal the need to expeditiously increase the availability of quantitative measures of nanomaterial hazard and broaden the sharing of that data and knowledge to support predictive modeling. In addition, research should continue to focus on methodologies for developing predictive models of nanomaterial hazard based on sub-lethal responses to low dose exposures.« less

  5. Comparative hazard analysis and toxicological modeling of diverse nanomaterials using the embryonic zebrafish (EZ) metric of toxicity

    SciTech Connect (OSTI)

    Harper, Bryan; Thomas, Dennis G.; Chikkagoudar, Satish; Baker, Nathan A.; Tang, Kaizhi; Heredia-Langner, Alejandro; Lins, Roberto D.; Harper, Stacey

    2015-06-04

    The integration of rapid assays, large data sets, informatics and modeling can overcome current barriers in understanding nanomaterial structure-toxicity relationships by providing a weight-of-the-evidence mechanism to generate hazard rankings for nanomaterials. Here we present the use of a rapid, low-cost assay to perform screening-level toxicity evaluations of nanomaterials in vivo. Calculated EZ Metric scores, a combined measure of morbidity and mortality, were established at realistic exposure levels and used to develop a predictive model of nanomaterial toxicity. Hazard ranking and clustering analysis of 68 diverse nanomaterials revealed distinct patterns of toxicity related to both core composition and outermost surface chemistry of nanomaterials. The resulting clusters guided the development of a predictive model of gold nanoparticle toxicity to embryonic zebrafish. In addition, our findings suggest that risk assessments based on the size and core composition of nanomaterials alone may be wholly inappropriate, especially when considering complex engineered nanomaterials. These findings reveal the need to expeditiously increase the availability of quantitative measures of nanomaterial hazard and broaden the sharing of that data and knowledge to support predictive modeling. In addition, research should continue to focus on methodologies for developing predictive models of nanomaterial hazard based on sub-lethal responses to low dose exposures.

  6. Efficacy and Toxicity of Chemoradiotherapy Using Intensity-Modulated Radiotherapy for Unknown Primary of Head and Neck

    SciTech Connect (OSTI)

    Sher, David J.; Balboni, Tracy A.; Haddad, Robert I.; Norris, Charles M.; Posner, Marshall R.; Wirth, Lori J.; Goguen, Laura A.; Annino, Donald; Tishler, Roy B.

    2011-08-01

    Purpose: No single standard treatment paradigm is available for head-and-neck squamous cell carcinoma of an unknown primary (HNCUP). Bilateral neck radiotherapy with mucosal axis irradiation is widely used, with or without chemotherapy and/or surgical resection. Intensity-modulated radiotherapy (IMRT) is a highly conformal method for delivering radiation that is becoming the standard of care and might reduce the long-term treatment-related sequelae. We report the Dana-Farber Cancer Institute experience with IMRT-based treatment for HNCUP. Patients and Materials: A retrospective study of all patients treated at the Dana-Farber Cancer Institute for HNCUP with IMRT between August 2004 and January 2009. The primary endpoint was overall survival; the secondary endpoints were locoregional and distant control, and acute and chronic toxicity. Results: A total of 24 patients with HNCUP were included. Of these patients, 22 had Stage N2 disease or greater. All patients underwent neck computed tomography, positron emission tomography-computed tomography, and examination under anesthesia with directed biopsies. Of the 24 patients, 22 received concurrent chemotherapy, and 7 (29%) also underwent induction chemotherapy. The median involved nodal dose was 70 Gy, and the median mucosal dose was 60 Gy. With a median follow-up of 2.1 years, the 2-year actuarial overall survival and locoregional control rate was 92% and 100%, respectively. Only 25% of the patients had Grade 2 xerostomia, although 11 patients (46%) required esophageal dilation for stricture. Conclusion: In a single-institution series, IMRT-based chemoradiotherapy for HNCUP was associated with superb overall survival and locoregional control. The xerostomia rates were promising, but the aggressive therapy was associated with significant rates of esophageal stenosis.

  7. Canadian Environmental Protection Act, strategic options for the management of toxic substances: Electric power generation (fossil fuel) sector, report of stakeholder consultations

    SciTech Connect (OSTI)

    1997-12-31

    The Electric Power Generation Sector Issue Table was formed to assess the management of toxic substances released from that sector, and more specifically, to develop (where warranted) goals, targets, and effective and efficient options for managing toxic releases in order to reduce potential risks to human health and the environment. This strategic options report sets out the recommendations of Issue Table members for the management of toxic substances. The introduction includes an industry profile and a review of the provincial management of electric power sector strategic options priority (SOP) substances. Chapter 2 discusses what substances are toxic, estimates releases of SOP substances from the sector, and reviews Issue Table approaches to risk assessment. Chapter 3 outlines Issue Table activities. Chapter 4 screens toxic substance management options, with evaluation of options against 13 groups of criteria. Chapter 5 presents toxic substances management proposals made to the Issue Table by the electric power generation industry, environmental groups, and Environment Canada.

  8. High e

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    e ne rgy data s am ple ● NuMI beam events provide an useful calibration sample ● Collected over 70K candidates before shutdown The highest energy events are prim arily from kaon decays. Two sam ples at high energy provide normalization and shape inform ation for kaon backgrounds to oscillation analysis: ● ν e events passing oscillation event selection cuts ● ν µ induced CCQE, CCπ+events Reconstructed neutrino energy EνQE(GeV) ν from other particles ν from pions ν from Kaons -

  9. Survival Fraction at 2 Gy and γH2AX Expression Kinetics in Peripheral Blood Lymphocytes From Cancer Patients: Relationship With Acute Radiation-Induced Toxicities

    SciTech Connect (OSTI)

    Pouliliou, Stamatia E.; Dimitriou, Thespis; Giatromanolaki, Alexandra; Papazoglou, Dimitrios; Pappa, Aglaia; Pistevou, Kyriaki

    2015-07-01

    Purpose: Predictive assays for acute radiation toxicities would be clinically relevant in radiation oncology. We prospectively examined the predictive role of the survival fraction at 2 Gy (SF2) and of γH2AX (double-strand break [DSB] DNA marker) expression kinetics in peripheral blood mononuclear cells (PBMCs) from cancer patients before radiation therapy. Methods and Materials: SF2 was measured with Trypan Blue assay in the PBMCs from 89 cancer patients undergoing radiation therapy at 4 hours (SF2{sub [4h]}) and 24 hours (SF2{sub [24h]}) after ex vivo irradiation. Using Western blot analysis and band densitometry, we further assessed the expression of γH2AX in PBMC DNA at 0 hours, 30 minutes, and 4 hours (33 patients) and 0 hour, 4 hours, and 24 hours (56 patients), following ex vivo irradiation with 2 Gy. Appropriate ratios were used to characterize each patient, and these were retrospectively correlated with early radiation therapy toxicity grade. Results: The SF2{sub (4h)} was inversely correlated with the toxicity grade (P=.006). The γH2AX-ratio{sub (30min)} (band density of irradiated/non-irradiated cells at 30 minutes) revealed, similarly, a significant inverse association (P=.0001). The DSB DNA repair rate from 30 minutes to 4 hours, calculated as the relative RγH2AX-ratio (γH2AX-ratio{sub (4h)}/γH2AX-ratio{sub (30min)}) showed a significant direct association with high toxicity grade (P=.01). Conclusions: Our results suggest that SF2 is a significant radiation sensitivity index for patients undergoing radiation therapy. γH2AX Western blot densitometry analysis provided 2 important markers of normal tissue radiation sensitivity. Low γH2AX expression at 30 minutes was linked with high toxicity grade, suggesting that poor γH2AX repair activity within a time frame of 30 minutes after irradiation predicts for poor radiation tolerance. On the other hand, rapid γH2AX content restoration at 4 hours after irradiation, compatible with

  10. Intensity-Modulated Radiotherapy as Primary Therapy for Prostate Cancer: Report on Acute Toxicity After Dose Escalation With Simultaneous Integrated Boost to Intraprostatic Lesion

    SciTech Connect (OSTI)

    Fonteyne, Valerie Villeirs, Geert; Speleers, Bruno; Neve, Wilfried de; Wagter, Carlos de; Lumen, Nicolas; Meerleer, Gert de

    2008-11-01

    Purpose: To report on the acute toxicity of a third escalation level using intensity-modulated radiotherapy for prostate cancer (PCa) and the acute toxicity resulting from delivery of a simultaneous integrated boost (SIB) to an intraprostatic lesion (IPL) detected on magnetic resonance imaging (MRI), with or without spectroscopy. Methods and Materials: Between January 2002 and March 2007, we treated 230 patients with intensity-modulated radiotherapy to a third escalation level as primary therapy for prostate cancer. If an IPL (defined by MRI or MRI plus spectroscopy) was present, a SIB was delivered to the IPL. To report on acute toxicity, patients were seen weekly during treatment and 1 and 3 months after treatment. Toxicity was scored using the Radiation Therapy Oncology Group toxicity scale, supplemented by an in-house-developed scoring system. Results: The median dose to the planning target volume was 78 Gy. An IPL was found in 118 patients. The median dose to the MRI-detected IPL and MRI plus spectroscopy-detected IPL was 81 Gy and 82 Gy, respectively. No Grade 3 or 4 acute gastrointestinal toxicity developed. Grade 2 acute gastrointestinal toxicity was present in 26 patients (11%). Grade 3 genitourinary toxicity was present in 15 patients (7%), and 95 patients developed Grade 2 acute genitourinary toxicity (41%). No statistically significant increase was found in Grade 2-3 acute gastrointestinal or genitourinary toxicity after a SIB to an IPL. Conclusion: The results of our study have shown that treatment-induced acute toxicity remains low when intensity-modulated radiotherapy to 80 Gy as primary therapy for prostate cancer is used. In addition, a SIB to an IPL did not increase the severity or incidence of acute toxicity.

  11. Heme oxygenase-1 protects endothelial cells from the toxicity of air pollutant chemicals

    SciTech Connect (OSTI)

    Lawal, Akeem O.; Zhang, Min; Dittmar, Michael; Lulla, Aaron; Araujo, Jesus A.

    2015-05-01

    Diesel exhaust particles (DEPs) are a major component of diesel emissions, responsible for a large portion of their toxicity. In this study, we examined the toxic effects of DEPs on endothelial cells and the role of DEP-induced heme oxygenase-1 (HO-1) expression. Human microvascular endothelial cells (HMECs) were treated with an organic extract of DEPs from an automobile engine (A-DEP) or a forklift engine (F-DEP) for 1 and 4 h. ROS generation, cell viability, lactate dehydrogenase leakage, expression of HO-1, inflammatory genes, cell adhesion molecules and unfolded protein respone (UPR) gene were assessed. HO-1 expression and/or activity were inhibited by siRNA or tin protoporphyrin (Sn PPIX) and enhanced by an expression plasmid or cobalt protoporphyrin (CoPPIX). Exposure to 25 μg/ml of A-DEP and F-DEP significantly induced ROS production, cellular toxicity and greater levels of inflammatory and cellular adhesion molecules but to a different degree. Inhibition of HO-1 enzymatic activity with SnPPIX and silencing of the HO-1 gene by siRNA enhanced DEP-induced ROS production, further decreased cell viability and increased expression of inflammatory and cell adhesion molecules. On the other hand, overexpression of the HO-1 gene by a pcDNA 3.1D/V5-HO-1 plasmid significantly mitigated ROS production, increased cell survival and decreased the expression of inflammatory genes. HO-1 expression protected HMECs from DEP-induced prooxidative and proinflammatory effects. Modulation of HO-1 expression could potentially serve as a therapeutic target in an attempt to inhibit the cardiovascular effects of ambient PM. - Highlights: • We examined the role of HO-1 expression on diesel exhaust particle (DEP) in endothelial cells. • DEPs exert cytotoxic and inflammatory effects on human microvascular endothelial cells (HMECs). • DEPs induce HO-1 expression in HMECs. • HO-1 protects against the oxidative stress induced by DEps. • HO-1 attenuates the proinflammatory effects

  12. PCB 126 toxicity is modulated by cross-talk between caveolae and Nrf2 signaling

    SciTech Connect (OSTI)

    Petriello, Michael C.; Han, Sung Gu; Newsome, Bradley J.; Hennig, Bernhard

    2014-06-01

    Environmental toxicants such as polychlorinated biphenyls (PCBs) have been implicated in the promotion of multiple inflammatory disorders including cardiovascular disease, but information regarding mechanisms of toxicity and cross-talk between relevant cell signaling pathways is lacking. To examine the hypothesis that cross-talk between membrane domains called caveolae and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathways alters PCB-induced inflammation, caveolin-1 was silenced in vascular endothelial cells, resulting in a decreased PCB-induced inflammatory response. Cav-1 silencing (siRNA treatment) also increased levels of Nrf2-ARE transcriptional binding, resulting in higher mRNA levels of the antioxidant genes glutathione s-transferase and NADPH dehydrogenase quinone-1 in both vehicle and PCB-treated systems. Along with this upregulated antioxidant response, Cav-1 siRNA treated cells exhibited decreased mRNA levels of the Nrf2 inhibitory protein Keap1 in both vehicle and PCB-treated samples. Silencing Cav-1 also decreased protein levels of Nrf2 inhibitory proteins Keap1 and Fyn kinase, especially in PCB-treated cells. Further, endothelial cells from wildtype and Cav-1 −/− mice were isolated and treated with PCB to better elucidate the role of functional caveolae in PCB-induced endothelial inflammation. Cav-1 −/− endothelial cells were protected from PCB-induced cellular dysfunction as evidenced by decreased vascular cell adhesion molecule (VCAM-1) protein induction. Compared to wildtype cells, Cav-1 −/− endothelial cells also allowed for a more effective antioxidant response, as observed by higher levels of the antioxidant genes. These data demonstrate novel cross-talk mechanisms between Cav-1 and Nrf2 and implicate the reduction of Cav-1 as a protective mechanism for PCB-induced cellular dysfunction and inflammation. - Highlights: • Reduction of caveolin-1 protein protects against polychlorinated biphenyl toxicity. • Decreasing

  13. Toxicity mitigation and solidification of municipal solid waste incinerator fly ash using alkaline activated coal ash

    SciTech Connect (OSTI)

    Ivan Diaz-Loya, E.; Allouche, Erez N.; Eklund, Sven; Joshi, Anupam R.; Kupwade-Patil, Kunal

    2012-08-15

    Highlights: Black-Right-Pointing-Pointer Incinerator fly ash (IFA) is added to an alkali activated coal fly ash (CFA) matrix. Black-Right-Pointing-Pointer Means of stabilizing the incinerator ash for use in construction applications. Black-Right-Pointing-Pointer Concrete made from IFA, CFA and IFA-CFA mixes was chemically characterized. Black-Right-Pointing-Pointer Environmentally friendly solution to IFA disposal by reducing its toxicity levels. - Abstract: Municipal solid waste (MSW) incineration is a common and effective practice to reduce the volume of solid waste in urban areas. However, the byproduct of this process is a fly ash (IFA), which contains large quantities of toxic contaminants. The purpose of this research study was to analyze the chemical, physical and mechanical behaviors resulting from the gradual introduction of IFA to an alkaline activated coal fly ash (CFA) matrix, as a mean of stabilizing the incinerator ash for use in industrial construction applications, where human exposure potential is limited. IFA and CFA were analyzed via X-ray fluorescence (XRF), X-ray diffraction (XRD) and Inductive coupled plasma (ICP) to obtain a full chemical analysis of the samples, its crystallographic characteristics and a detailed count of the eight heavy metals contemplated in US Title 40 of the Code of Federal Regulations (40 CFR). The particle size distribution of IFA and CFA was also recorded. EPA's Toxicity Characteristic Leaching Procedure (TCLP) was followed to monitor the leachability of the contaminants before and after the activation. Also images obtained via Scanning Electron Microscopy (SEM), before and after the activation, are presented. Concrete made from IFA, CFA and IFA-CFA mixes was subjected to a full mechanical characterization; tests include compressive strength, flexural strength, elastic modulus, Poisson's ratio and setting time. The leachable heavy metal contents (except for Se) were below the maximum allowable limits and in many cases

  14. Compound-specific effects of diverse neurodevelopmental toxicants on global gene expression in the neural embryonic stem cell test (ESTn)

    SciTech Connect (OSTI)

    Theunissen, P.T.; Robinson, J.F.; Department of Toxicogenomics, Maastricht University, Maastricht; Netherlands Toxicogenomics Centre, Maastricht ; Pennings, J.L.A.; Netherlands Toxicogenomics Centre, Maastricht ; Herwijnen, M.H. van; Kleinjans, J.C.S.; Netherlands Toxicogenomics Centre, Maastricht ; Piersma, A.H.; Netherlands Toxicogenomics Centre, Maastricht; Institute for Risk Assessment Sciences, Faculty of Veterinary Sciences, Utrecht University, Utrecht

    2012-08-01

    Alternative assays for developmental toxicity testing are needed to reduce animal use in regulatory toxicology. The in vitro murine neural embryonic stem cell test (ESTn) was designed as an alternative for neurodevelopmental toxicity testing. The integration of toxicogenomic-based approaches may further increase predictivity as well as provide insight into underlying mechanisms of developmental toxicity. In the present study, we investigated concentration-dependent effects of six mechanistically diverse compounds, acetaldehyde (ACE), carbamazepine (CBZ), flusilazole (FLU), monoethylhexyl phthalate (MEHP), penicillin G (PENG) and phenytoin (PHE), on the transcriptome and neural differentiation in the ESTn. All compounds with the exception of PENG altered ESTn morphology (cytotoxicity and neural differentiation) in a concentration-dependent manner. Compound induced gene expression changes and corresponding enriched gene ontology biological processes (GO–BP) were identified after 24 h exposure at equipotent differentiation-inhibiting concentrations of the compounds. Both compound-specific and common gene expression changes were observed between subsets of tested compounds, in terms of significance, magnitude of regulation and functionality. For example, ACE, CBZ and FLU induced robust changes in number of significantly altered genes (≥ 687 genes) as well as a variety of GO–BP, as compared to MEHP, PHE and PENG (≤ 55 genes with no significant changes in GO–BP observed). Genes associated with developmentally related processes (embryonic morphogenesis, neuron differentiation, and Wnt signaling) showed diverse regulation after exposure to ACE, CBZ and FLU. In addition, gene expression and GO–BP enrichment showed concentration dependence, allowing discrimination of non-toxic versus toxic concentrations on the basis of transcriptomics. This information may be used to define adaptive versus toxic responses at the transcriptome level.

  15. High Efficiency Integrated Package

    SciTech Connect (OSTI)

    Ibbetson, James

    2013-09-15

    Solid-state lighting based on LEDs has emerged as a superior alternative to inefficient conventional lighting, particularly incandescent. LED lighting can lead to 80 percent energy savings; can last 50,000 hours – 2-50 times longer than most bulbs; and contains no toxic lead or mercury. However, to enable mass adoption, particularly at the consumer level, the cost of LED luminaires must be reduced by an order of magnitude while achieving superior efficiency, light quality and lifetime. To become viable, energy-efficient replacement solutions must deliver system efficacies of ≥ 100 lumens per watt (LPW) with excellent color rendering (CRI > 85) at a cost that enables payback cycles of two years or less for commercial applications. This development will enable significant site energy savings as it targets commercial and retail lighting applications that are most sensitive to the lifetime operating costs with their extended operating hours per day. If costs are reduced substantially, dramatic energy savings can be realized by replacing incandescent lighting in the residential market as well. In light of these challenges, Cree proposed to develop a multi-chip integrated LED package with an output of > 1000 lumens of warm white light operating at an efficacy of at least 128 LPW with a CRI > 85. This product will serve as the light engine for replacement lamps and luminaires. At the end of the proposed program, this integrated package was to be used in a proof-of-concept lamp prototype to demonstrate the component’s viability in a common form factor. During this project Cree SBTC developed an efficient, compact warm-white LED package with an integrated remote color down-converter. Via a combination of intensive optical, electrical, and thermal optimization, a package design was obtained that met nearly all project goals. This package emitted 1295 lm under instant-on, room-temperature testing conditions, with an efficacy of 128.4 lm/W at a color temperature of ~2873

  16. Analysis of 1994 Air Force toxic release inventory reporting. Master`s thesis

    SciTech Connect (OSTI)

    Pollock, B.A.

    1995-12-01

    The purpose of this research is to analyze the Air Force`s 1994 Toxic Release Inventory data. Statistical tests were used to meet the following research objectives: (1) review the CY 94 data to determine which chemicals were most often reported and which bases and major commands had the most releases in terms of the number of chemicals reported and the amount of chemicals reported and (2) investigate factors which could influence the reporting status of a facility. An analysis of a survey of Air Force facilities indicated that two factors had an influence on the reporting status of Air Force facilities: (1) whether the TRI point of contact had confidence in the completeness of the data used for threshold computations and (2) whether the primary database used for threshold computations was the Standard Base Supply System.

  17. Exposure of children to heavy metals from smelters: epidemiology and toxic consequences

    SciTech Connect (OSTI)

    Landrigan, P.J.; Baker, E.L.

    1981-06-01

    To evaluate the epidemiologic and toxicologic consequences of environmental exposure to heavy metals, we examined populations of children living near 21 primary, nonferrous metal smelters in the United States. Biological levels of heavy metals in these populations were related inversely to distance of residence from the smelting plants and were in direct proportion to levels of environmental contamination. Inhalation and ingestion of heavy metal particulates emitted by the smelters into air, soil, and dust were the principal causes of increased absorption. Elevated levels of erythrocyte protoporphyrin, as well as anemia and slowed motor nerve conduction velocity were the dose-related toxic consequences of lead absorption observed in the children studied. These data illustrate the importance of smelters as point sources of heavy metal contamination and as models for epidemiologic study.

  18. Mass-transport models to predict toxicity of inhaled gases in the upper respiratory tract

    SciTech Connect (OSTI)

    Hubal, E.A.C.; Fedkiw, P.S.; Kimbell, J.S. [North Carolina State Univ., Raleigh, NC (United States)

    1996-04-01

    Mass-transport (the movement of a chemical species) plays an important role in determining toxic responses of the upper respiratory tract (URT) to inhaled chemicals. Mathematical dosimetry models incorporate physical characteristics of mass transport and are used to predict quantitative uptake (absorption rate) and distribution of inhaled gases and vapors in the respiratory tract. Because knowledge of dose is an essential component of quantitative risk assessment, dosimetry modeling plays an important role in extrapolation of animal study results to humans. A survey of existing mathematical dosimetry models for the URT is presented, limitations of current models are discussed, and adaptations of existing models to produce a generally applicable model are suggested. Reviewed URT dosimetry models are categorized as early, lumped-parameter, and distributed-parameter models. Specific examples of other relevant modeling work are also presented. 35 refs., 11 figs., 1 tab.

  19. Subtask 1.11 -- Spectroscopic field screening of hazardous waste and toxic spills. Final report

    SciTech Connect (OSTI)

    Grisanti, A.A.

    1997-10-01

    Techniques for the field characterization of soil contamination due to spillage of hazardous waste or toxic chemicals are time-consuming and expensive. Thus more economical, less time-intensive methods are needed to facilitate rapid field screening of contaminated sites. The overall objective of this project is to study the feasibility of using an evanescent field absorbance sensor Fourier transform infrared spectroscopic sensor coupled with cone penetrometry as a field screening method. The specific objectives of this project are as follows: design an accessory for use with FT-IR that interfaces the spectrometer to a cone penetrometer; characterize the response of the FT-IR accessory to selected hydrocarbons in a laboratory-simulated field environment; and determine the ability of the FT-IR-CPT instrument to measure hydrocarbon contamination in soil by direct comparison with a reference method (e.g., Soxhlet extraction followed by gas chromatography) to quantify hydrocarbons from the same soil.

  20. The uranium from seawater program at PNNL: Overview of marine testing, adsorbent characterization, adsorbent durability, adsorbent toxicity, and deployment studies

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Gill, Gary A.; Kuo, Li -Jung; Janke, Christopher James; Park, Jiyeon; Jeters, Robert T.; Bonheyo, George T.; Pan, Horng -Bin; Wai, Chien; Khangaonkar, Tarang P.; Bianucci, Laura; et al

    2016-02-07

    at Woods Hole Oceanographic Institution with the ORNL AF1 adsorbent produced 15% and 55% higher adsorption capacities than observed at PNNL for column and flume testing, respectively. Variations in competing ions may be the explanation for the regional differences. In addition to marine testing, a number of other efforts are underway to characterize adsorbents and impacts of deployment on the marine environment. Highlights include: Hydrodynamic modelling predicts that a farm of adsorbent materials will likely have minimal effect on ocean currents and removal of uranium and other elements from seawater when densities are < 1800 braids/km2. A decrease in U adsorption capacity of up to 30% was observed after 42 days of exposure due to biofouling when the ORNL braided adsorbent AI8 was exposed to raw seawater in a flume in the presence of light. An identical raw seawater exposure with no light exposure showed little or no impact to adsorption capacity from biofouling. No toxicity was observed with column effluents of any absorbent materials tested to date. Toxicity could be induced with some non amidoxime-based absorbents only when the ratio of solid absorbent to test media was increased to highly unrealistic levels. Thermodynamic modeling of the seawater-amidoxime adsorbent was performed using the geochemical modeling program PHREEQC. Modeling of the binding of Ca, Mg, Fe, Ni, Cu, U, and V from batch interactions with seawater across a variety of concentrations of the amidoxime binding group reveal that when binding sites are limited (1 x 10-8 binding sites/kg seawater), vanadium heavily out-competes other ions for the amidoxime sites. In contrast, when binding sites are abundant magnesium and calcium dominate the total percentage of metals bound to the sorbent.« less

  1. Intervention of D-glucose ameliorates the toxicity of streptozotocin in accessory sex organs of rat

    SciTech Connect (OSTI)

    Vikram, A.; Tripathi, D.N.; Ramarao, P.; Jena, G.B.

    2008-01-01

    Streptozotocin (STZ) is a naturally occurring compound isolated from Streptomyces achromogens. It is used extensively for inducing diabetes in experimental animals. Diabetes mellitus is known to have proven adverse effects on male sexual organs and their reproductive functions. The atrophy of prostate gland and other organs of the genitourinary tract were observed in experimental diabetic animals. STZ exhibits a structural resemblance to D-glucose due to the presence of sugar moiety in its structure. Pancreatic {beta}-cells mainly contain GLUT1 and GLUT2 glucose transporters. Possibly due to structural resemblance, STZ and D-glucose, share a common recognition site for entry into the {beta}-cells. The objective of the present study is to evaluate the effect of D-glucose on STZ-induced toxicity in accessory sex organs of male rats. Animals were kept on overnight fasting. One group received vehicle and served as negative control, while all other groups were given STZ (45 mg/kg). Animals that received only STZ served as positive control. The effect of D-glucose was studied on STZ treated animals with different dosage of D-glucose (250, 500, 1000 and 2000 mg/kg). Restoration of body weight, plasma glucose and plasma insulin was evident only at 1000 and 2000 mg/kg of D-glucose. The protective effect of D-glucose is evident only when it is administered simultaneously with STZ. In the present investigation, we report that simultaneous administration of D-glucose along with STZ ameliorates STZ-induced toxicity. This is evident from the restoration of accessory sex organ's weight, cellular morphology as well as insulin level.

  2. Toxic substances from coal combustion -- A comprehensive assessment. Quarterly report, October 1, 1996--December 31, 1996

    SciTech Connect (OSTI)

    Bool, L.E. III; Senior, C.L.; Huggins, F.; Huffman, G.P.; Shah, N.

    1997-01-31

    The Clean Air Act Amendments of 1990 identify a number of hazardous air pollutants (HAPs) as candidates for regulation. Should regulations be imposed on HAP emissions from coal-fired power plants, a sound understanding of the fundamental principles controlling the formation and partitioning of toxic species during coal combustion will be needed. With support from the Federal Energy Technology Center (FETC), the Electric Power Research Institute, and VTT (Finland), Physical Sciences Inc. (PSI) has teamed with researchers from USGS, MIT, the University of Arizona (UA), the University of Kentucky (UKy), the University of Connecticut, and Princeton University to develop a broadly applicable emissions model useful to regulators and utility planners. The new Toxics Partitioning Engineering Model (ToPEM) will be applicable to all combustion conditions including new fuels and coal blends, low-NOx combustion systems, and new power generation plants. Development of ToPEM will be based on PSI`s existing Engineering Model for Ash Formation (EMAF). During the past quarter the final program coal, from the Wyodak seam in the Powder River Basin, was acquired and distributed. Extensive coal characterization and laboratory work is underway to develop and test new sub-models. Coal characterization in the past quarter included direct identification of the modes of occurrence of various trace inorganic species in coal and ash using unique analytical techniques such as XAFS analysis and selective leaching. Combustion testing of the bituminous coals continued and additional data were obtained on trace element vaporization in the combustion zone. Studies of post-combustion trace element transformations, such as mercury speciation in the flue gas, were also begun in the last quarter.

  3. Acute Esophagus Toxicity in Lung Cancer Patients After Intensity Modulated Radiation Therapy and Concurrent Chemotherapy

    SciTech Connect (OSTI)

    Kwint, Margriet; Uyterlinde, Wilma; Nijkamp, Jasper; Chen, Chun; Bois, Josien de; Sonke, Jan-Jakob; Heuvel, Michel van den; Knegjens, Joost; Herk, Marcel van; Belderbos, Jose

    2012-10-01

    Purpose: The purpose of this study was to investigate the dose-effect relation between acute esophageal toxicity (AET) and the dose-volume parameters of the esophagus after intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with non-small cell lung cancer (NSCLC). Patients and Methods: One hundred thirty-nine patients with inoperable NSCLC treated with IMRT and concurrent chemotherapy were prospectively analyzed. The fractionation scheme was 66 Gy in 24 fractions. All patients received concurrently a daily dose of cisplatin (6 mg/m Superscript-Two ). Maximum AET was scored according to Common Toxicity Criteria 3.0. Dose-volume parameters V5 to V70, D{sub mean} and D{sub max} of the esophagus were calculated. A logistic regression analysis was performed to analyze the dose-effect relation between these parameters and grade {>=}2 and grade {>=}3 AET. The outcome was compared with the clinically used esophagus V35 prediction model for grade {>=}2 after radical 3-dimensional conformal radiation therapy (3DCRT) treatment. Results: In our patient group, 9% did not experience AET, and 31% experienced grade 1 AET, 38% grade 2 AET, and 22% grade 3 AET. The incidence of grade 2 and grade 3 AET was not different from that in patients treated with CCRT using 3DCRT. The V50 turned out to be the most significant dosimetric predictor for grade {>=}3 AET (P=.012). The derived V50 model was shown to predict grade {>=}2 AET significantly better than the clinical V35 model (P<.001). Conclusions: For NSCLC patients treated with IMRT and concurrent chemotherapy, the V50 was identified as most accurate predictor of grade {>=}3 AET. There was no difference in the incidence of grade {>=}2 AET between 3DCRT and IMRT in patients treated with concurrent chemoradiation therapy.

  4. Proton Beam Craniospinal Irradiation Reduces Acute Toxicity for Adults With Medulloblastoma

    SciTech Connect (OSTI)

    Brown, Aaron P.; Barney, Christian L.; Grosshans, David R.; McAleer, Mary Frances; Groot, John F. de; Puduvalli, Vinay K.; Tucker, Susan L.; Crawford, Cody N.; Khan, Meena; Khatua, Soumen; Gilbert, Mark R.; Brown, Paul D.; Mahajan, Anita

    2013-06-01

    Purpose: Efficacy and acute toxicity of proton craniospinal irradiation (p-CSI) were compared with conventional photon CSI (x-CSI) for adults with medulloblastoma. Methods and Materials: Forty adult medulloblastoma patients treated with x-CSI (n=21) or p-CSI (n=19) at the University of Texas MD Anderson Cancer Center from 2003 to 2011 were retrospectively reviewed. Median CSI and total doses were 30.6 and 54 Gy, respectively. The median follow-up was 57 months (range 4-103) for x-CSI patients and 26 months (range 11-63) for p-CSI. Results: p-CSI patients lost less weight than x-CSI patients (1.2% vs 5.8%; P=.004), and less p-CSI patients had >5% weight loss compared with x-CSI (16% vs 64%; P=.004). p-CSI patients experienced less grade 2 nausea and vomiting compared with x-CSI (26% vs 71%; P=.004). Patients treated with x-CSI were more likely to have medical management of esophagitis than p-CSI patients (57% vs 5%, P<.001). p-CSI patients had a smaller reduction in peripheral white blood cells, hemoglobin, and platelets compared with x-CSI (white blood cells 46% vs 55%, P=.04; hemoglobin 88% vs 97%, P=.009; platelets 48% vs 65%, P=.05). Mean vertebral doses were significantly associated with reductions in blood counts. Conclusions: This report is the first analysis of clinical outcomes for adult medulloblastoma patients treated with p-CSI. Patients treated with p-CSI experienced less treatment-related morbidity including fewer acute gastrointestinal and hematologic toxicities.

  5. Toxicity studies on Agents GB and GD (Phase 2): 90-day subchronic study of GB (Sarin, Type I) in CD rats. Final report, Jul 85-Aug 91

    SciTech Connect (OSTI)

    Bucci, T.J.; Parker, R.M.; Crowell, J.A.; Thurman, J.D.; Gosnell, P.A.

    1991-08-01

    A two-phase Dose Range finding study and a 90-Day Subchronic study were conducted in CD rats using the organophosphate ester Sarin (Agent GB, Type I, CAS Number 107-44-8). The highest dose level without lethality in the second phase of the range finding study was designated the maximum tolerated dose (MTD). The doses selected for the subchronic study were the MTD (300 micron GBI/Kg/day), MTD/2 (150, micron GBI/Kg/day), MTD/4 (75 micron GBI/Kg/day), and a vehicle control (O micron /Kg/day). Forty-eight male and forty-eight female CD rats were randomly allocated at 11-12 weeks of age into four treatment groups (12 per sex per group). The animals were gavaged Monday through Friday for 13 weeks and euthanized with carbon dioxide at the beginning of the fourteenth week. Animals were observed daily for clinical signs of toxicity and were weighed weekly. The rats were bled (6 rats/sex/dose) during weeks -1, 1, 3, 7, and at necropsy. Necropsy examination was performed on all animals. Microscopic evaluation was performed on all high-dose and control animals, and on those tissues of lower dose animals that were abnormal at necropsy. All gross lesions and all animals dying or removed early received histological examination. A cause of death or morbidity for animals removed before the end of the study, determined from histopathological examination, was established in four of the eight cases. There were several statistically significant effects in the clinical chemistry and hematology data. These effects were scattered among the treatment groups and were not numerous enough to develop a pattern of organ toxicity.

  6. Oil-spill cleanup agent efficacy, toxicity, and biodegradation: An annotated bibliography, 1984-1991. Final report

    SciTech Connect (OSTI)

    Tjeerdema, R.S.; Smalheer, D.L.; Jacobson, S.

    1992-03-01

    The annotated bibliography presents literature published between 1984 and 1991 on the environmental fate of petroleum and on all aspects of petroleum and cleanup agent toxicology, including toxicity, effectiveness, biodegradation and analytical methodology. Abstracts and a subject index are provided to facilitate specific searches. The project was supported by the California Department of Fish and Game, Office of Oil Spill Prevention and Response.

  7. Building Toxic Metal Characterization and Decontamination Report: Area 6, Building 914

    SciTech Connect (OSTI)

    NSTec Industrial Hygiene

    2011-08-15

    The purpose of this report is to outline the toxic metal characterization and decontamination efforts in Area 6, Building 914. This includes the initial building inspection, the hotspot sampling, results/findings, building cleanup, and the verification sampling. Building 914 is a steel light frame building that was constructed in 1992. It is about 16,454 square feet, and five employees are assigned to this building. According to the building's floor plan blueprints, it could be inferred that this building was once a Wiremen/Lineman shop. In 2002-2004, the National Nuclear Security Administration Nevada Site Office embarked on a broad characterization of beryllium (Be) surface concentrations throughout the North Las Vegas Facility, the Nevada National Security Site (NNSS), and ancillary facilities like the Special Technologies Laboratory, Remote Sensing Laboratory, etc. Building 914 was part of this characterization. The results of the 2002 study illustrated that the metal housekeeping limits were within acceptable limits and from a Be standpoint, the building was determined to be fit for occupancy. On March 2, 2011, based on a request from Building 914 users, National Security Technologies, LLC (NSTec) Industrial Hygiene (IH) collected bulk samples from the southwest corner of Building 914 at heights above 6 feet where black dust had been noticed on this particular wall. IH conducted surface swipe sampling of the area and analyzed the samples for toxic metals, namely, beryllium (Be), cadmium (Cd), chromium (Cr), lead (Pb), and manganese (Mn). The sample results indicated values two to four times above the housekeeping threshold for Be, Cd, Cr, Pb, and Mn. Subsequently, the facility was closed and posted; the necessary personnel were notified; and controls were instituted for ingress and egress of the building. On March 17, 2011, IH performed an extensive sampling event involving the entire warehouse in accordance with NSTec Organization Procedure OP-P250

  8. Fluoride-elicited developmental testicular toxicity in rats: Roles of endoplasmic reticulum stress and inflammatory response

    SciTech Connect (OSTI)

    Zhang, Shun; Jiang, Chunyang; Liu, Hongliang; Guan, Zhizhong; Zeng, Qiang; Zhang, Cheng; Lei, Rongrong; Xia, Tao; Gao, Hui; Yang, Lu; Chen, Yihu; Wu, Xue; Zhang, Xiaofei; Cui, Yushan; Yu, Linyu; Wang, Zhenglun; Wang, Aiguo

    2013-09-01

    Long-term excessive fluoride intake is known to be toxic and can damage a variety of organs and tissues in the human body. However, the molecular mechanisms underlying fluoride-induced male reproductive toxicity are not well understood. In this study, we used a rat model to simulate the situations of human exposure and aimed to evaluate the roles of endoplasmic reticulum (ER) stress and inflammatory response in fluoride-induced testicular injury. SpragueDawley rats were administered with sodium fluoride (NaF) at 25, 50 and 100 mg/L via drinking water from pre-pregnancy to gestation, birth and finally to post-puberty. And then the testes of male offspring were studied at 8 weeks of age. Our results demonstrated that fluoride treatment increased MDA accumulation, decreased SOD activity, and enhanced germ cell apoptosis. In addition, fluoride elevated mRNA and protein levels of glucose-regulated protein 78 (GRP78), inositol requiring ER-to-nucleus signal kinase 1 (IRE1), and C/EBP homologous protein (CHOP), indicating activation of ER stress signaling. Furthermore, fluoride also induced testicular inflammation, as manifested by gene up-regulation of tumor necrosis factor-? (TNF-?), interleukin-1? (IL-1?), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in a nuclear factor-?B (NF-?B)-dependent manner. These were associated with marked histopathological lesions including injury of spermatogonia, decrease of spermatocytes and absence of elongated spermatids, as well as severe ultrastructural abnormalities in testes. Taken together, our results provide compelling evidence that ER stress and inflammation would be novel and significant mechanisms responsible for fluoride-induced disturbance of spermatogenesis and germ cell loss in addition to oxidative stress. - Highlights: We used a rat model to simulate the situations of human fluoride (F) exposure. Developmental F exposure induces testicular damage related with oxidative stress. Endoplasmic

  9. Unexpected gender difference in sensitivity to the acute toxicity of dioxin in mice

    SciTech Connect (OSTI)

    Pohjanvirta, Raimo; Miettinen, Hanna; Sankari, Satu; Hegde, Nagabhooshan; Lindn, Jere; Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, FI-00014 University of Helsinki

    2012-07-15

    The acute toxicity of the ubiquitous environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) varies widely among species and strains. Previous studies in rats have established that females are approximately 2-fold more sensitive to TCDD lethality than males. However, there is a surprising gap in the literature regarding possible gender-related sensitivity differences in mice. In the present study, by using three substrains of TCDD-sensitive C57BL/6 mice and transgenic mice on this background, we demonstrated that: 1) in contrast to the situation in rats, female mice are the more resistant gender; 2) the magnitude of the divergence between male and female mice depends on the substrain, but can amount to over 10-fold; 3) AH receptor protein expression levels or mutations in the primary structure of this receptor are not involved in the resistance of female mice of a C57BL/6 substrain, despite their acute LD{sub 50} for TCDD being over 5000 ?g/kg; 4) transgenic mice that globally express the rat wildtype AH receptor follow the mouse type of gender difference; 5) in gonadectomized mice, ovarian estrogens appear to enhance TCDD resistance, whereas testicular androgens seem to augment TCDD susceptibility; and 6) the gender difference correlates best with the severity of liver damage, which is also reflected in hepatic histopathology and the expression of pro-inflammatory cytokines, especially IL-6. Hence, the two closely related rodent species most often employed in toxicological risk characterization studies, rat and mouse, represent opposite examples of the influence of gender on dioxin sensitivity, further complicating the risk assessment of halogenated aromatic hydrocarbons. -- Highlights: ? In contrast to rats, male mice are more sensitive to TCDD toxicity than female mice. ? The resistance of female C57BL/6Kuo mice matches or exceeds that of male DBA/2 mice. ? The resistance of female C57BL/6Kuo mice is not based on AHR structure or abundance. ? Both

  10. Multi-parameter in vitro toxicity testing of crizotinib, sunitinib, erlotinib, and nilotinib in human cardiomyocytes

    SciTech Connect (OSTI)

    Doherty, Kimberly R.; Wappel, Robert L.; Talbert, Dominique R.; Trusk, Patricia B.; Moran, Diarmuid M.; Kramer, James W.; Brown, Arthur M.; Shell, Scott A.; Bacus, Sarah

    2013-10-01

    Tyrosine kinase inhibitors (TKi) have greatly improved the treatment and prognosis of multiple cancer types. However, unexpected cardiotoxicity has arisen in a subset of patients treated with these agents that was not wholly predicted by pre-clinical testing, which centers around animal toxicity studies and inhibition of the human Ether--go-go-Related Gene (hERG) channel. Therefore, we sought to determine whether a multi-parameter test panel assessing the effect of drug treatment on cellular, molecular, and electrophysiological endpoints could accurately predict cardiotoxicity. We examined how 4 FDA-approved TKi agents impacted cell viability, apoptosis, reactive oxygen species (ROS) generation, metabolic status, impedance, and ion channel function in human cardiomyocytes. The 3 drugs clinically associated with severe cardiac adverse events (crizotinib, sunitinib, nilotinib) all proved to be cardiotoxic in our in vitro tests while the relatively cardiac-safe drug erlotinib showed only minor changes in cardiac cell health. Crizotinib, an ALK/MET inhibitor, led to increased ROS production, caspase activation, cholesterol accumulation, disruption in cardiac cell beat rate, and blockage of ion channels. The multi-targeted TKi sunitinib showed decreased cardiomyocyte viability, AMPK inhibition, increased lipid accumulation, disrupted beat pattern, and hERG block. Nilotinib, a second generation Bcr-Abl inhibitor, led to increased ROS generation, caspase activation, hERG block, and an arrhythmic beat pattern. Thus, each drug showed a unique toxicity profile that may reflect the multiple mechanisms leading to cardiotoxicity. This study demonstrates that a multi-parameter approach can provide a robust characterization of drug-induced cardiomyocyte damage that can be leveraged to improve drug safety during early phase development. - Highlights: TKi with known adverse effects show unique cardiotoxicity profiles in this panel. Crizotinib increases ROS, apoptosis, and