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Toxic Chemicals (toxic + chemical)
Selected AbstractsTK/TD dose,response modeling of toxicityENVIRONMETRICS, Issue 5 2007Munni Begum Abstract In environmental cancer risk assessment of a toxic chemical, the main focus is in understanding induced target organ toxicity that may in turn lead to carcinogenicity. Mathematical models based on systems of ordinary differential equations with biologically relevant parameters are tenable methods for describing the disposition of chemicals in target organs. In evaluation of a toxic chemical, dose,response assessment often addresses only toxicodynamics (TD) of the chemical, while its toxicokinetics (TK) do not enter into consideration. The primary objective of this research is to integrate both TK and TD in evaluation of toxic chemicals while performing dose,response assessment. Population models, with hierarchical setup and nonlinear predictors, for TK concentration and TD effect measures are considered. A one-compartment model with biologically relevant parameters, such as organ volume, uptake rate and excretion rate, or clearance, is used to derive the TK predictor while a two parameter Emax model is used as a predictor for TD measures. Inference of the model parameters with nonnegative and assay's Limit of Detection (LOD) constraints was carried out by Bayesian approaches using Markov Chain Monte Carlo (MCMC) techniques. Copyright © 2006 John Wiley & Sons, Ltd. [source] Nitric oxide in inflammatory bowel disease: a universal messenger in an unsolved puzzleIMMUNOLOGY, Issue 4 2004George Kolios Summary In recent years, nitric oxide (NO), a gas previously considered to be a potentially toxic chemical, has been established as a diffusible universal messenger that mediates cell,cell communication throughout the body. Constitutive and inducible NO production regulate numerous essential functions of the gastrointestinal mucosa, such as maintenance of adequate perfusion, regulation of microvascular and epithelial permeability, and regulation of the immune response. Up-regulation of the production of NO via expression of inducible nitric oxide synthase (iNOS) represents part of a prompt intestinal antibacterial response; however, NO has also been associated with the initiation and maintenance of inflammation in human inflammatory bowel disease (IBD). Recent studies on animal models of experimental IBD have shown that constitutive and inducible NO production seems to be beneficial during acute colitis, but sustained up-regulation of NO is detrimental. This fact is also supported by studies on mice genetically deficient in various NOS isoforms. However, the mechanism by which NO proceeds from being an indispensable homeostatic regulator to a harmful destructor remains unknown. Furthermore, extrapolation of data from animal colitis models to human IBD is questionable. The purpose of this review is to update our knowledge about the role of this universal mediator and the enzymes that generate it in the pathogenesis of IBD. [source] Neuropathic pain: symptoms, models, and mechanismsDRUG DEVELOPMENT RESEARCH, Issue 4 2006Simon Beggs Abstract Peripheral neuropathic pain is the most debilitating of all clinical pain syndromes and affects a large and growing number of people worldwide. There are diverse causes for peripheral neuropathic pain, which may be experienced after traumatic nerve injury or from diseases that affect peripheral nerves, such as diabetes, HIV/AIDS, and cancer, and it can also result from toxic chemicals, such as cancer chemotherapy agents. Despite these varying causes, it is clear that neuropathic pain is due to persistent pathological alterations resulting in hyperexcitability in the peripheral and central nervous systems, and it is the neuropathology that must be targeted for effective therapy of which there is none presently available. Mechanistically, neuropathic pain is distinct from acute pain and inflammatory pain, for which many effective therapies are known. In this review, we describe the relationships between clinical symptoms and experimental models of peripheral neuropathic pain, and we provide a framework for understanding the potential mechanisms that involve primary neuronal dysfunction as well as pathological changes in neuron-glial signaling. Drug Dev. Res. 67:289,301, 2006. © 2006 Wiley-Liss, Inc. [source] Detergent-induced cell aggregation in subpopulations of Pseudomonas aeruginosa as a preadaptive survival strategyENVIRONMENTAL MICROBIOLOGY, Issue 9 2007Janosch Klebensberger Summary During growth of Pseudomonas aeruginosa strain PAO1 with the toxic detergent SDS, a part of the population actively formed macroscopic cell aggregates while the other part grew as freely suspended cells. The physiological function of aggregation for growth with SDS was investigated. Three mutants growing with SDS without aggregation were isolated: the spontaneous mutant strain N and two mutants with transposon insertions in the psl operon for exopolysaccharide synthesis. SDS-induced aggregation in strain N but not in a pslJ mutant was restored by complementation with two genes encoding diguanylate cyclases responsible for synthesis of cyclic-di-guanosine monophosphate (c-di-GMP). By expressing a c-di-GMP-specific phosphodiesterase SDS-induced aggregation of strain PAO1 was reduced. Upon exposure to SDS in the presence of the uncoupler carbonyl cyanide chlorophenylhydrazone, the aggregating strains had ca. 500-fold higher survival rates than the non-aggregating strains. Co-incubation experiments revealed that strain N could integrate into aggregates of strain PAO1 and thereby increase its survival rate more than 1000-fold. These results showed that SDS-induced aggregation involved c-di-GMP signalling with the psl operon as a possible target. Cell aggregation could serve as a pre-adaptive strategy ensuring survival and growth of P. aeruginosa populations in environments with multiple toxic chemicals. [source] Fractal analysis of Daphnia motion for acute toxicity bioassayENVIRONMENTAL TOXICOLOGY, Issue 5 2002Nobuaki Shimizu Abstract To quantify individual behavioral responses to toxic chemicals, the swimming motion of individual Daphniamagna was continuously monitored using a motion analysis system. The fractal dimension was introduced to compare the straightness or complexity of the swimming trajectory before and after exposure to toxic chemicals. Analysis indicated that the swimming trajectory of individual Daphnia has a fractal structure. The basal fractal dimension in the control medium was 1.35±0.01 (n = 50 Daphnia). Exposure to CuSO4 (10 ,g/L), organophosphorus (Dichlorvos; 10 ,g/L), and carbamate (Propoxur; 500 ,g/L) pesticide caused a significant increase in the fractal dimension with a latency of 60 min, reaching a maximal level of 2.26±0.34, 2.43±0.19, and 2.51±0.21, respectively, after a 120-min exposure. The magnitude of the change in the fractal dimension was related to the toxic chemical concentration and the exposure time. Threshold concentrations determined at 60 min of exposure were 10 ,g/L for CuSO4, 5 ,g/L for Dichlorvos, and 500 ,g/L for Propoxur. The toxicity index (EC50) values after 120 min of exposure were 6.31 ,g/L, 7.64 ,g/L, and 466 ,g/L for CuSO4, Dichlorvos, and Propoxur, respectively. Thus, the fractal dimension seems useful for analyzing and comparing complex trails, such as swimming trajectories, which could be used as the endpoint for an acute bioassay. © 2002 Wiley Periodicals, Inc. Environ Toxicol 17: 441,448, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/tox.10077 [source] Development of a daphnia magna DNA microarray for evaluating the toxicity of environmental chemicalsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2007Hajime Watanabe Abstract Toxic chemical contaminants have a variety of detrimental effects on various species, and the impact of pollutants on ecosystems has become an urgent issue. However, the majority of studies regarding the effects of chemical contaminants have focused on vertebrates. Among aquatic organisms, Daphnia magna has been used extensively to evaluate organism- and populationlevel responses of invertebrates to pollutants in acute toxicity or reproductive toxicity tests. Although these types of tests can provide information concerning hazardous concentrations of chemicals, they provide no information about their mode of action. Recent advances in molecular genetic techniques have provided tools to better understand the responses of aquatic organisms to pollutants. In the present study, we adapted some of the techniques of molecular genetics to develop new tools, which form the basis for an ecotoxicogenomic assessment of D. magna. Based on a Daphnia expressed sequence tag database, we developed an oligonucleotide-based DNA microarray with high reproducibility. The DNA microarray was used to evaluate gene expression profiles of neonatal daphnids exposed to several different chemicals: Copper sulfate, hydrogen peroxide, pentachlorophenol, or ,-naphthoflavone. Exposure to these chemicals resulted in characteristic patterns of gene expression that were chemical-specific, indicating that the Daphnia DNA microarray can be used for classification of toxic chemicals and for development of a mechanistic understanding of chemical toxicity on a common freshwater organism. [source] Relationship between lysosomal membrane destabilization and chemical body burden in eastern oysters (Crassostrea virginica) from Galveston Bay, Texas, USAENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2002Hyun-Min Hwang Abstract Lysosomal destabilization was measured by using hemocytes of eastern oysters (Crassostrea virginica) collected along a chemical concentration gradient in Galveston Bay, Texas, USA. Results of the lysosomal response were compared to concentrations of organic compounds and trace elements in oyster tissue. Concentrations (on a dry-wt basis) ranged from 288 to 2,390 ng/g for polycyclic aromatic hydrocarbons (PAHs), 38 to 877 ng Sn/g for tri- n -butyltin (TBT), 60 to 562 ng/g for polyclorinated biphenyls (PCBs), and 7 to 71 ng/g for total DDT. Trace element concentrations (on a dry-wt basis) ranged from 1.1 to 4.0 ,g/g for Cd, 105 to 229 ,g/g for Cu, 212 to 868 ,g/g for Al, and 1,200 to 8,180 ,g/g for Zn. The percentage of destabilized lysosomes ranged from 34 to 81%. A significant positive correlation (p < 0.05) was observed between lysosomal destabilization and body burden of organic compounds (PAHs, PCBs, TBT, and chlorinated pesticides). No significant correlation was found between metal concentrations and lysosomal destabilization. Based on lysosomal destabilization, the study sites in Galveston Bay can be placed in one of three groups: healthy (Hanna Reef and Confederate Bay), moderately damaged (Offats Bayou and Todd's Dump), and highly damaged (Yacht Club and Ship Channel). Lysosomal destabilization that is consistent with toxic chemical body burdens supports previous observations that lysosomal membranes are damaged by toxic chemicals and indicates that this method can serve as an early screening tool to assess overall ecosystem health by using oysters. [source] What level of effect is a no observed effect?ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2000Mark Crane Abstract The no observed effect concentration (NOEC) is currently a major summary statistic in ecotoxicity testing. Its use is heavily criticized, partly because it is a poor estimator of "safe" chemical concentrations. In this short communication, we review the limited information available on the percentage effect that corresponds with the NOEC, a value designated the ECNOEC, and calculate ECNOEC values for fish growth data. The average ECNOEC for different test protocols was found to vary widely, with values for chronic studies ranging from 10 to 34%. Individual results varied even more widely. This analysis suggests that the NOEC is neither a consistent summary statistic nor an indicator of safe concentrations of toxic chemicals. [source] TK/TD dose,response modeling of toxicityENVIRONMETRICS, Issue 5 2007Munni Begum Abstract In environmental cancer risk assessment of a toxic chemical, the main focus is in understanding induced target organ toxicity that may in turn lead to carcinogenicity. Mathematical models based on systems of ordinary differential equations with biologically relevant parameters are tenable methods for describing the disposition of chemicals in target organs. In evaluation of a toxic chemical, dose,response assessment often addresses only toxicodynamics (TD) of the chemical, while its toxicokinetics (TK) do not enter into consideration. The primary objective of this research is to integrate both TK and TD in evaluation of toxic chemicals while performing dose,response assessment. Population models, with hierarchical setup and nonlinear predictors, for TK concentration and TD effect measures are considered. A one-compartment model with biologically relevant parameters, such as organ volume, uptake rate and excretion rate, or clearance, is used to derive the TK predictor while a two parameter Emax model is used as a predictor for TD measures. Inference of the model parameters with nonnegative and assay's Limit of Detection (LOD) constraints was carried out by Bayesian approaches using Markov Chain Monte Carlo (MCMC) techniques. Copyright © 2006 John Wiley & Sons, Ltd. [source] Bioterrorism: Introduction and Major AgentsJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 11 2001Charles Kemp FNP It is not if, but where and when. In light of the September 11 World Trade Center and Pentagon attacks, biological terrorist acts in the United States seem more likely than ever before. We know there are people willing to die to kill Americans and we know that nations with a history of supporting terrorism have biological warfare (BW) capability. Some of the states capable of BW include Iraq, Libya, Syria, and Iran,all of which have close ties to transnational terrorist groups such as Al-Qaeda, Armed Islamic Group of Algeria, and Al-Jihad of Egypt (Davis, 1999; McGovern, Christopher, & Eitzen, 1999; Sanger, & Kahn, 2001). The threat is not limited to these nations or groups, but all do present a clear danger. According to the U.S. Central Intelligence Agency, operatives of Al-Qaeda (the Osama bin Laden group) "have trained to conduct attacks with toxic chemicals or biological toxins" (Broad, & Peterson, 2001). [source] Sediment dynamics and pollutant mobility in rivers: An interdisciplinary approachLAKES & RESERVOIRS: RESEARCH AND MANAGEMENT, Issue 1 2004Ulrich Förstner Abstract Characteristic dynamic features of sediment-related processes in rivers include dramatic effects of stormwater events on particle transport, rapid and far-reaching effects of sulphide oxidation during resuspension, and biological accumulation and potential release of toxic chemicals. Pollutant mobility is the net result of the stabilizing and mobilizing effects in both hydraulic and chemical fields. In practice, emphasis has to be given to fine-grained sediments and suspended matter as these materials exhibit large surface areas and high sorption capacities. Organic materials are highly reactive. Degradation of organic matter will induce oxygen depletion and might enhance formation of flocs and biofilms. Study of variations of sediment and water chemistry should predominantly include changes of pH and redox conditions, competition of dissolved ions and processes such as complexation by organic substances. Major questions relate to the potential reduction of sorption sites on minerals and degradation of organic carrier materials. All these processes will influence solution/solid equilibrium conditions and have to be studied prior to modelling the overall effects of pollutants on the water body and aquatic ecosystems. With respect to handling and remediation of contaminated river sediments, either in-place or excavated, a chemical and biological characterization of the material, of the (disposal) site and of the long-term processes is crucial. Passive techniques (e.g. in situ stabilization, subaqueous capping) provide economic advantages as there are no operation costs following their installation. However, the success of these ecological and geochemical engineering approaches is mainly based on an in-depth knowledge of the underlying processes. [source] Reducing water erosion in a gypsic soil by combined use of organic amendment and shrub revegetationLAND DEGRADATION AND DEVELOPMENT, Issue 4 2005M. J. Marqués Abstract Degraded gypsic soils in the centre of Spain can be rehabilitated with organic amendment and shrub revegetation. Erosion has been measured on plots of 2×0·5,m2 under simulated rainfall of 70,mm,h,1 and a kinetic energy of 18,J,mm,1,m,2. Samples of water runoff and sediments were studied in the summer of the years 2002 and 2003. The presence of shrub Atriplex halimus (Chenonodiaceae) significantly reduces runoff from 16·9 to 6·7,ml,m,2,min,1 and sediments from 0·16 to 0·02,g,m,2,min,1. When sewage sludge is applied the differences among plots with and without bushes disappear. Although both treatments independently applied are efficient as erosion control measures, the combined use of revegetation and organic amendment allows a reduced dose of sewage sludge with the same effect on erosion. A low dose of sludge is desirable in view of the accumulation of toxic chemicals. Copyright © 2005 John Wiley & Sons, Ltd. [source] Rhizoremediation of lindane by root-colonizing SphingomonasMICROBIAL BIOTECHNOLOGY, Issue 1 2008Dietmar Böltner Summary We used a two-step enrichment approach to isolate root-colonizing hexachlorocyclohexane (HCH)-degrading microorganisms. The first step consists of the use of classical liquid enrichment to isolate ,-HCH degraders. The ,-HCH-degrading microbes were attached in mass to corn seeds sown in soil with ,-HCH, and after plant development we rescued bacteria growing on root tips. Bacteria were then subjected to a second enrichment round in which growth on liquid medium with ,-HCH and inoculation of corn seeds were repeated. We then isolated bacteria on M9 minimal medium with ,-HCH from root tips. We were able to isolate four Sphingomonas strains, all of which degraded ,-, ,-, ,- and ,-HCH. Two of the strains were particularly good colonizers of corn roots, reaching high cell density in vegetated soil and partly removing ,-HCH. In contrast, these bacteria performed poorly in unplanted soils. This study supports the hypothesis that the removal of persistent toxic chemicals can be accelerated by combinations of plants and bacteria, a process generally known as rhizoremediation. [source] Cohort mortality study of Philadelphia firefightersAMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 5 2001Dalsu Baris MD Abstract Background Fire fighters are exposed to a wide variety of toxic chemicals. Previous studies have reported excess risk of some cancers but have been limited by small numbers or little information on employment characteristics. Methods We conducted a retrospective cohort mortality study among 7,789 Philadelphia firefighters employed between 1925 and 1986. For each cause of death, the standardized mortality ratios (SMRs) and 95% confidence intervals were estimated. We also compared mortality among groups of firefighters defined by the estimated number of career runs and potential for diesel exposure. Results In comparison with U.S. white men, the firefighters had similar mortality from all causes of death combined (SMR,=,0.96) and all cancers (SMR,=,1.10). There were statistically significant deficits of deaths from nervous system diseases (SMR,=,0.47), cerebrovascular diseases (SMR,=,0.83), respiratory diseases (SMR,=,0.67), genitourinary diseases (SMR,=,0.54), all accidents (SMR,=,0.72), and suicide (SMR,=,0.66). Statistically significant excess risks were observed for colon cancer (SMR,=,1.51) and ischemic heart disease (SMR,=,1.09). The risks of mortality from colon cancer (SMR,=,1.68), kidney cancer (SMR,=,2.20), non-Hodgkin's lymphoma (SMR,=,1.72), multiple myeloma (SMR,=,2.31), and benign neoplasms (SMR,=,2.54) were increased among firefighters with at least 20 years of service. Conclusions Our study found no significant increase in overall mortality among Philadelphia firefighters. However, we observed increased mortality for cancers of the colon and kidney, non-Hodgkin's lymphoma and multiple myeloma. There was insufficient follow-up since the introduction of diesel equipment to adequately assess risk. Am. J. Ind. Med. 39:463,476, 2001. Published 2001 Wiley-Liss, Inc. [source] Detoxification of the explosive 2,4,6-trinitrotoluene in Arabidopsis: discovery of bifunctional O - and C -glucosyltransferasesTHE PLANT JOURNAL, Issue 6 2008Fernando Gandia-Herrero Summary Plants, as predominantly sessile organisms, have evolved complex detoxification pathways to deal with a diverse range of toxic chemicals. The elasticity of this stress response system additionally enables them to tackle relatively recently produced, novel, synthetic pollutants. One such compound is the explosive 2,4,6-trinitrotoluene (TNT). Large areas of soil and groundwater are contaminated with TNT, which is both highly toxic and recalcitrant to degradation, and persists in the environment for decades. Although TNT is phytotoxic, plants are able to tolerate low levels of the compound. To identify the genes involved in this detoxification process, we used microarray analysis and then subsequently characterized seven uridine diphosphate (UDP) glycosyltransferases (UGTs) from Arabidopsis thaliana (Arabidopsis). Six of the recombinantly expressed UGTs conjugated the TNT-transformation products 2- and 4-hydroxylaminodinitrotoulene, exhibiting individual bias for either the 2- or the 4-isomer. For both 2- and 4-hydroxylaminodinitrotoulene substrates, two monoglucose conjugate products, confirmed by HPLC-MS-MS, were observed. Further analysis indicated that these were conjugated by either an O - or C -glucosidic bond. The other major compounds in TNT metabolism, aminodinitrotoluenes, were also conjugated by the UGTs, but to a lesser extent. These conjugates were also identified in extracts and media from Arabidopsis plants grown in liquid culture containing TNT. Overexpression of two of these UGTs, 743B4 and 73C1, in Arabidopsis resulted in increases in conjugate production, and enhanced root growth in 74B4 overexpression seedlings. Our results show that UGTs play an integral role in the biochemical mechanism of TNT detoxification by plants. [source] Influence of Hyperglycaemia on Chemical-Induced Toxicity: Study with Cyclophosphamide in RatBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2009Kalavatala Saandeep Hyperglycaemia perturbs the critical balance between oxidative stress and anti-oxidant defence mechanisms in the body and thereby alters the response of biological system towards various toxic chemicals. Cyclophosphamide (CP) is a widely prescribed anticancer drug, well-known genotoxic agent as well as used in the development of immunocompromised animal models. The present study investigated the modulating effect of diabetes on the cyclophosphamide-induced cytotoxicity and genotoxicity. The study was performed on male Sprague-Dawley rats (200 ± 10 g). Cyclophosphamide (10 mg/kg) was administered five consecutive days in a week for 3 weeks to both control and diabetic rats. Thiobarbituric acid reactive substances (TBARS) levels were measured in the plasma, liver, kidney and lung tissues. DNA damaging potential of cyclophosphamide under diabetic condition was evaluated using comet and halo assay as an endpoint. To further ascertain the mode of cell death, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay and immunohistochemical evaluation of p53 was performed. Significant increase in DNA damage was revealed by the comet assay parameters, halo assay indicated the level of cytotoxicity and the oxidative stress was measured using the TBARS assay in the diabetic rats receiving cyclophosphamide treatment. The toxic effects were more prominent in diabetic animals as compared to non-diabetic rats. Cyclophosphamide treatment and diabetic condition per se led to increase in the p53 + and TUNEL + cells in the liver and kidney of rats. Under diabetic condition, further increase in the p53 + and TUNEL + cells was observed in response to cyclophosphamide. In the present study, we report that hyperglycaemic condition exaggerates the cyclophosphamide-induced toxicity and the response was found to be tissue specific. [source] Industrial and agricultural pollution: a threat to the health of children living in the Arctic regionACTA PAEDIATRICA, Issue 11 2003R ZetterströmArticle first published online: 2 JAN 200 Various environmental pollutants of industrial or agricultural origin such as persistent organic pollutants (POCs) are causing great concern owing to their toxicity to humans and animals. At the Stockholm Convention on POCs in 2001, 12 of these pollutants, i.e. dioxins, PCBs (polychlorinated biphenyls) and DDT were referred to as "the dirty dozen". Conclusion: Collaborative studies by scientists from Canada, Russia, Scandinavia and other countries representing different fields such as environmental chemistry, ecology and medical sciences may increase our knowledge about the present threat of toxic chemicals to ecology and human health in the Arctic region. It is hoped that improved understanding will promote preventive political decisions. [source] |