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Increased acetone exhalation induced by metabolites of halogenated C1 and C2 compounds.

Rats were exposed, in a closed desiccator jar chamber, to concentrations of various halogenated C1 and C2 compounds at which the metabolizing capacities were saturated (Vmax conditions). Within the exposure period of 50 h concentrations of the xenobiotic and of exhaled acetone were monitored in the gas phase of the system. The quantitative extent of acetone exhalation was dependent on the individual compound examined. Acetone exhalation was stimulated in presence of vinyl chloride, vinyl bromide, vinyl fluoride, vinylidene fluoride, cis- and trans-1,2-dichloroethylene, trichloroethylene, perchloroethylene, methylene chloride, chloroform, carbon tetrachloride and 1,1,2-trichloroethane. No stimulation of acetone exhalation occurred with 1,1,1-trichloroethane and with the reference hydrocarbon n-hexane. Also, acetone exhalation was evoked by infusions of either fluoroacetate or chloroacetate, two anticipated or proven metabolites of some haloethylenes; the infusion rates of which were based on calculations of the metabolic rates of vinylidene fluoride and of vinyl chloride, respectively.

Acetone↗

The Desulfitobacterium genus.

Desulfitobacterium spp. are strictly anaerobic bacteria that were first isolated from environments contaminated by halogenated organic compounds. They are very versatile microorganisms that can use a wide variety of electron acceptors, such as nitrate, sulfite, metals, humic acids, and man-made or naturally occurring halogenated organic compounds. Most of the Desulfitobacterium strains can dehalogenate halogenated organic compounds by mechanisms of reductive dehalogenation, although the substrate spectrum of halogenated organic compounds varies substantially from one strain to another, even with strains belonging to the same species. A number of reductive dehalogenases and their corresponding gene loci have been isolated from these strains. Some of these loci are flanked by transposition sequences, suggesting that they can be transmitted by horizontal transfer via a catabolic transposon. Desulfitobacterium spp. can use H2 as electron donor below the threshold concentration that would allow sulfate reduction and methanogenesis. Furthermore, there is some evidence that syntrophic relationships occur between Desulfitobacterium spp. and sulfate-reducing bacteria, from which the Desulfitobacterium cells acquire their electrons by interspecies hydrogen transfer, and it is believed that this relationship also occurs in a methanogenic consortium. Because of their versatility, desulfitobacteria can be excellent candidates for the development of anaerobic bioremediation processes. The release of the complete genome of Desulfitobacterium hafniense strain Y51 and information from the partial genome sequence of D. hafniense strain DCB-2 will certainly help in predicting how desulfitobacteria interact with their environments and other microorganisms, and the mechanisms of actions related to reductive dehalogenation.

Biodegradation, Environmental↗

Clinical significance of atomic inner shell ionization (ISI) and Auger cascade for radiosensitization using IUdR, BUdR, platinum salts, or gadolinium porphyrin compounds.

PURPOSE: Halogenated pyrimidines (iododeoxyuridine [IUdR] and bromodeoxyuridine [BUdR]), platinum salts, and gadolinium porphyrins are heavy atom compounds used as radiosensitizers. For IUdR, it has been hypothesized that iodine inner shell ionizations (ISI) and Auger cascades could be one of the primary radiosensitization mechanisms. The purpose of this paper is to estimate the number of ISI produced per tumor cell and per 2 Gy irradiation in clinically relevant modelings. MATERIALS AND METHODS: ISI were evaluated using a two-step method. Photon-induced ISI were calculated using the MCNP-4C Monte Carlo code, heavy atom concentrations from clinical data published in the literature, and at various depths in a water phantom irradiated with 6-MV, (60)Co, (137)Cs, or (192)Ir sources. Electron knock-on induced ISI on K, L, and M atomic shells were evaluated with an hybrid method, using simulated electron spectra and cross-sections derived from the Møller formalism. Using a biological dose equivalence of 0.05 Gy per cell ISI, relative biological effectiveness (RBE) values were calculated for each situation. RESULTS: For platinum and gadolinium, ISI occurs in far less than 0.1% of the cell, whichever is the configuration. For IUdR and BUdR, ISI occurs in between 45% to 483% of the cell. Due to spectrum degradation, about 3 times more photoelectric ISI are generated at greater than shallower depths, and 10 times more for (192)Ir compared with (60)Co or 6-MV X-rays. Photoelectric ISI are about 3 times more frequent for iodine than bromine, but electron knock-on ISI are more frequent on bromine, and at the end about the same number of ISI are generated for both elements. RBEs were found to be between 1.01 and 1.12 for clinically relevant irradiation settings. CONCLUSIONS: The mechanisms of radiosensitization for platinum and gadolinium are clearly not related to an Auger cascade. For halogenated pyrimidines, however, clinically relevant numbers of ISI are generated within each cell. For IUdR, ISI appears to be strongly tied to the photon spectra. Halogenated pyrimidines should be evaluated again clinically, but using lower energy photons like a (192)Ir implant.

Bromodeoxyuridine↗

Anaerobic dehalogenation of organohalide contaminants in the marine environment.

Microbially mediated dehalogenation processes contribute to the global cycling of both biogenic and anthropogenic halogenated organic compounds. Detailed information on biodegradation mechanisms for a variety of organohalides and on the microorganisms mediating these processes has greatly increased our understanding of the cycling and fate of these unique and widespread compounds in our environment. The marine environment appears to be a particularly rich source of dehalogenating microorganisms. It is well established by laboratory and field studies that anaerobic dehalogenation of sediment contaminants, such as PCBs, pesticides, and dioxins, occurs intrinsically and can be enhanced via various methods. Specific dehalogenating bacterial populations can be enriched on various organohalides. Biodehalogenation processes are likely to be significantly affected by the prevailing terminal electron-accepting condition, and thus, biotransformation of organohalide contaminants in marine and estuarine environments will vary as a function of the redox conditions within the sediment profile. Fundamental knowledge of the activities and interactions of dehalogenating microorganisms is providing a strong basis for development of new bioremediation technologies for removal of harmful halogenated compounds from our environment.

Anaerobiosis↗

Quantitative structure-property relationship study on reductive dehalogenation of selected halogenated aliphatic hydrocarbons in sediment slurries.

In this study, by the use of partial least squares (PLS) method and 26 quantum chemical descriptors computed by PM3 Hamiltonian, a quantitative structure-property relationship (QSPR) model was developed for reductive dehalogenation rate constants of 13 halogenated aliphatic compounds in sediment slurry under anaerobic conditions. The model can be used to explain the dehalogenation mechanism. Halogenated aliphatic compounds with great energy of the lowest unoccupied molecular orbital (Elumo), total energy (TE), electronic energy (EE), the smallest bond order of the carbon-halogen bonds (BO) and the most positive net atomic charges on an atom of the molecule (q+) values tend to be reductively dehalogenated slow, whereas halogenated aliphatic compounds with high values of molecular weight (Mw), average molecular polarizability (alpha) and core-core repulsion energy (CCR) values tend to be reductively dehalogenated fastest.

Electrons↗

Toxicological effects of disinfections using sodium hypochlorite on aquatic organisms and its contribution to AOX formation in hospital wastewater.

Sodium hypochlorite (NaOCl) is often used for disinfecting hospital wastewater in order to prevent the spread of pathogenic microorganisms, causal agents of nosocomial infectious diseases. Chlorine disinfectants in wastewater react with organic matters, giving rise to organic chlorine compounds such as AOX (halogenated organic compounds adsorbable on activated carbon), which are toxic for aquatic organisms and are persistent environmental contaminants. The aim of this study was to evaluate the toxicity on aquatic organisms of hospital wastewater from services using NaOCl in pre-chlorination. Wastewater samples from the infectious and tropical diseases department of a hospital of a large city in southeast of France were collected. Three samples per day were collected in the connecting well department at 9 a.m., 1 p.m. and 5 p.m. during 8 days from 13 March to 22 March 2001, and a mixture was made at 6 p.m. with the three samples in order to obtain a representative sample for the day. The toxicity test comprised the 24-h EC50 on Daphnia magna and a bioluminescence assay using Vibrio fischeri photobacteria. Fecal coliforms and physicochemical analyses such as total organic carbon (TOC), chloride, AOX, total suspended solids (TSS) and chemical oxygen demand (COD) were carried out. Wastewater samples highlighted considerable acute toxicity on D. magna and V. fischeri photobacteria. However, low most probable numbers (MPN), ranging from <3 to 2400 for 100 ml, were detected for fecal coliforms. Statistical analysis, with a confidence interval of 95%, gave a strong linear regression assessed with r=0.98 between AOX concentrations and EC50 (TU) on daphnia. The identification of an ideal concentration of NaOCl in disinfecting hospital wastewater, i.e. its non-observed effect concentration (NOEC) on algae and D. magna, seems to be a research issue that could facilitate the control of AOX toxicity effects on aquatic organisms. Therefore, it would be necessary to monitor the biocide properties of NaOCl on fecal coliforms at various doses and its toxicity effects on aquatic organisms.

Animals↗

Synthesis and antimicrobial activity of some novel derivatives of benzofuran: part 1. Synthesis and antimicrobial activity of (benzofuran-2-yl)(3-phenyl-3-methylcyclobutyl) ketoxime derivatives.

The reaction of salicylaldehyde with 1-phenyl-1-methyl-3-(2-chloro-1-oxoethyl) cyclobutane (1) and potassium carbonate was used to prepare (benzofuran-2-yl)(3-methyl-3-phenylcyclobutyl) methanone (2) for the starting reagent purposes. (benzofuran-2-yl)(3-phenyl-3-methyl cyclobutyl) ketoxime (3) was synthesized from the reaction of the compound (2) with hidroxylamine. New derivatives of (benzofuran-2-yl)(3-phenyl-3-methyl cyclobutyl) ketoxime (3) such as, O-glycidylketoxime (4) and O-phenylacylketoxime (5a-c) were obtained very high yields. Alkyl, allyl and aryl substituted N-oxime ethers (6a-e) were obtained from the reaction compound 3 and various halogen contained compounds. The syntheses of the compounds (7a-f) were carried out from the reaction of the compound (4) and different amines such as, isopropyl amine, natrium azide, morpholine and piperazine. All of the synthesized compounds were tested for antimicrobial activity against Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 1539, Salmonella typhi, Shigella flexneri, Proteus mirabilis ATCC 14153 and Candida albicans ATCC 10231. Among the synthesized compounds (benzofuran-2-yl)(3-phenyl-3-methyl cyclobutyl)-O-[2-hydroxy-3-(N-methylpiperazino)] propylketoxime (7d) was found the most active derivative against S. aureus ATCC 6538. The compounds 2, 5b, 6b, 6c, 7b and 7f showed very strong and the same antimicrobial effect against C. albicans ATCC 10231. Similarly (benzofuran-2-yl)(3-phenyl-3-methylcyclobutyl)-O-benzylketoxime 6a showed good antimicrobial effect against C. albicans ATCC 10231. None of the other compounds exhibited activity against the other test microorganisms.

Anti-Infective Agents↗

Alfred Werner revisited: the coordination chemistry of anions.

A series of macrocyclic receptors were designed to probe the influence of four factors, hydrogen bonding, charge, dimensionality, and topology, on anion binding. Monocyclic and bicyclic polyammonium and polyamide receptors were synthesized from either 2,2'-diaminodiethylamine derivatives (dien) or 2,2',2''-aminoethylamine (tren) building blocks, plus aromatic or heterocyclic spacers. Supramolecular complexes of these hosts with three simple anion topologies were probed: spherical (halides), trigonal planar (nitrate), and tetrahedral (sulfate). Results indicate a number of corollaries with transition-metal coordination chemistry in terms of binding concepts such as the chelate effect and dual valencies, as well as geometries for anion complexes that are strikingly similar to those observed in transition-metal coordination chemistry.

Anions↗

Nicotinic acetylcholine receptors and imaging.

In vivo imaging techniques like positron emission tomography (PET) and single photon emission computed tomography (SPECT) offer the possibility to monitor human central nicotinic acetylcholine receptors (nAChRs) in a variety of central nervous system disorders. In the past, the only available PET radiotracer for imaging nAChRs in the human brain, [11C]-(-)-nicotine, suffered from a spectrum of not suitable properties for in vivo imaging. Current efforts are focused on the development of new, highly specific and highly selective radioligands based on different structural classes (e.g. nicotine, epibatidine, 3-pyridyl ether analogues) for central nAChRs. The most promising compounds are halogenated 3-pyridyl ether compounds for imaging alpha 4 beta 2 nAChRs. But there is still a lack for radiotracers for other subtypes of nicotinic acetylcholine receptors being a promising area of interest.

Animals↗

A hierarchical coding system for occupational exposure.

A 10-digit hierarchical method for coding occupationally encountered chemicals offering significant advantages over existing chemical coding systems has been developed and tested. With this unique system, substances are categorized and coded according to their composition and physical natures. Consequently, compounds of similar structure may be distinguished, and classes of similar compounds (for example, all halogenated organic compounds, all inorganic sulfates) can be readily retrieved. This novel coding system was developed to assist primarily in the identification of potential carcinogens in occupational studies using job exposure matrices. However, the system has wider applications as it can be employed by industry to facilitate data management and monitoring programs in the workplace.

Carcinogens↗

[Structure-activity relationships of halogenated phenylethanolamine and phenoxypropanolamine].

12 compounds from the series of halogenated phenylethanolamines and phenoxypropanolamines were tested at the isolated rabbit jejunum, and the pD2-and pA2-values were determined. All the substances act beta-adrenolytically. Except for 3,4-dichloronoradrenaline, which stimulates the alpha-receptors, all the compounds still have pronounced beta-mimetic effects. The 2,5-dihalogenated phenylethanolamines and phenoxypropanolamines block the beta-receptors at lower concentrations than 2,4-dihalogen derivatives. The weakest beta-adrenolytic effects at the intestine were found with compounds halogenated at the 3,4-position.

Adrenergic beta-Antagonists↗

Comparative study of aqueous and non-aqueous capillary electrophoresis in the separation of halogenated phenolic and bisphenolic compounds in water samples.

Capillary zone electrophoresis methods, based on either aqueous and non-aqueous solutions as running buffers and UV spectrophotometric detection, have been developed and optimized for the separation of several halogenated phenolic and bisphenolic compounds, suspected or proved to exhibit hormonal disrupting effects. Both aqueous capillary electrophoresis (CE) and non-aqueous capillary electrophoresis (NACE) methods were suitable for the analysis of compounds under study. The separation of the analytes from other 25 potentially interfering phenolic derivatives was achieved with NACE method. Large-volume sample stacking using the electroosmotic flow pump (LVSEP) was assayed as on-column preconcentration technique for sensitivity enhancement. LVSEP-CE and LVSEP-NACE improved peak heights by 5-26 and 16-330 folds, respectively. To evaluate their applicability, the capillary electrophoresis methods developed were applied to the analysis of water samples, using solid-phase extraction as sample pre-treatment process.

Electrophoresis, Capillary↗

An experimental and computational study on the effect of Al(OiPr)3 on atom-transfer radical polymerization and on the catalyst-dormant-chain halogen exchange.

Compound Al(OiPr)3 is shown to catalyze the halide-exchange process leading from [Mo(Cp)Cl2(iPrN=CH-CH=NiPr)] and CH3CH(X)COOEt (X=Br, I) to the mixed-halide complexes [Mo(Cp)ClX(iPrN=CH-CH=NiPr)]. On the other hand, no significant acceleration is observed for the related exchange between [MoX3(PMe3)3] (X=Cl, I) and PhCH(Br)CH3, by analogy to a previous report dealing with the Ru(II) complex [RuCl2(PPh3)3]. A DFT computation study, carried out on the model complexes [Mo(Cp)Cl2(PH3)2], [MoCl3(PH3)3], and [RuCl2(PH3)3], and on the model initiators CH3CH(Cl)COOCH3, CH3Cl, and CH3Br, reveals that the 16-electron Ru(II) complex is able to coordinate the organic halide RX in a slightly exothermic process to yield saturated, diamagnetic [RuCl2(PH3)3(RX)] adducts. The 15-electron [MoCl3(PH3)3] complex is equally capable of forming an adduct, that is, the 17-electron [MoCl3(PH3)3(CH3Cl)] complex with a spin doublet configuration, although the process is endothermic, because it requires an energetically costly electron-pairing process. The interaction between the 17-electron [Mo(Cp)Cl2(PH3)2] complex and CH3Cl, on the other hand, is repulsive and does not lead to a stable 19-electron adduct. The [RuCl2(PH3)3(CH3X)] system leads to an isomeric complex [RuClX(PH3)3(CH3Cl)] by internal nucleophilic substitution at the carbon atom. The transition state of this process for X=Cl (degenerate exchange) is located at lower energy than the transition state required for halogen-atom transfer leading to [RuCl3(PH3)3] and the free radical CH3. On the basis of these results, the uncatalyzed halide exchange is interpreted as the result of a competitive S(N)i process, whose feasibility depends on the electronic configuration of the transition-metal complex. The catalytic action of Al(OiPr)3 on atom-transfer radical polymerization (and on halide exchange for the 17-electron half-sandwich Mo(III) complex) results from a more favorable Lewis acid-base interaction with the oxidized metal complex, in which the transferred halogen atom is bound to a more electropositive element. This conclusion derives from DFT studies of the model [Al(OCH3)3]n (n=1,2,3,4) compounds, and on the interaction of Al(OCH3)3 with CH3Cl and with the [Mo(Cp)Cl3(PH3)2] and [RuCl3(PH3)3] complexes.

Journal Article↗

Organochlorine pesticides and polychlorinated biphenyls in human adipose tissue.

Halogenated organic compounds are highly lipophilic chemicals that are persistent in the environment as a result of their use and chemical stability. Some of these compounds are also present in the environment as metabolites or oxidation products of a parent compound or as by-products formed in the production of chlorinated compounds. Chronic exposure to the general population results mainly through the food chain. Because they are lipophilic, and because many are metabolized slowly, these chemicals tend to concentrate in body fat tissue. This contribution has described these halogenated organic compounds, discussed their use, regulation and prohibition throughout the world, and reviewed published studies on the levels of these chemicals found in the adipose tissue of humans and animals. For many years, residues of halogenated organic compounds have been detected in the human adipose tissue of individuals in a number of countries, including those in Europe, Asia, and Africa, as well as in the U.S. The levels detected have been used as an index of the level of general population exposure of these compounds over time. Over the past two decades, most countries have observed a steady decline of this level of exposure, reflecting a reduction in the use of these compounds, restrictions on or banning of their use, and a corresponding decrease in their environmental levels. The levels of concentrations vary from chemical to chemical as well as from isomer to isomer. Since the use of aldrin and dieldrin has now been banned or restricted in the U.S. and a number of other countries, residue levels have slowly decreased. Mean values in human adipose tissue in the U.S. and some foreign countries ranged from 0.04 to 0.40 ppm for dieldrin. Aldrin was detected only in Argentina and Poland in the 1970s and endrin was not detected anywhere at anytime. By 1978, all products containing BHC registered in the U.S. has been either discontinued or reformulated to incorporate lindane rather than BHC. The potential for exposure to BHC is virtually nonexistent in the U.S.; however, exposure to lindane is possible since products containing this chemical are still marketed, and used particularly in the manufacture of human medicine. DDT was banned for agricultural purposes in the U.S. in 1972, although it is still used elsewhere for public health vector control. Since the decline in use of DDT, however, the average levels of concentration have also declined. Heptachlor, chlordane, and trans-nonachlor (a component of both heptachlor and chlordane) are chlorinated cyclodienes.(ABSTRACT TRUNCATED AT 400 WORDS)

Adipose Tissue↗

[Organohalogen contamination of a dialysis-water treatment plant].

On March 2001 the regular quality control test of the water used for dialysis in an urban centre using a reverse osmosis system revealed a high level of organo-halogenated contamination. The compounds implicated were: trichloroethylene (trielene) [M.Wt. 131 D], tetrachloroethylene, trichloromethane (chloroform) [M.Wt. 121 D], chlorodibromomethane. The dialysis unit was closed. Water samples were analysed in duplicate. The table shows the values (in ppm or microgram/l) obtained for chloroform at the given times: March 8th, altered sample; March 12th, confirmation sample; March 16th, after osmosis membranes change; March 22nd, after carbon filtration replacement; March 26th, after softener resins substitution. The AAMI doesn't recommend any value for organo-halogenated compounds in dialysis water. In the past, the European Pharmacopoeia and the Italian Health Ministry released some reference values for tap water, values which were extended to water used for dialysis. The values are 1 ppm as reference value, 30 ppm as maximum accepted value for the sum of all organo-halogenated compounds, and 10 ppm as the recommended value. In conclusion, the problem was solved by progressive replacement of the components of the water treatment system, even though the real cause remained undetermined. No clinical symptom was recorded and no level of chloroform or trielene was detected in patients' sera despite the low molecular weight and low protein binding of the compounds. A strict control of the water quality and a more comprehensive and updated reference guide are needed for better and safer dialysis delivery.

Charcoal↗

Biotransformations catalyzed by the genus Rhodococcus.

Rhodococci display a diverse range of metabolic capabilities and they are a ubiquitous feature of many environments. They are able to degrade short-chain, long-chain, and halogenated hydrocarbons, and numerous aromatic compounds, including halogenated and other substituted aromatics, heteroaromatics, hydroaromatics, and polycyclic aromatic hydrocarbons. They possess a wide variety of pathways for degrading and modifying aromatic compounds, including dioxygenase and monooxygenase ring attack, and cleavage of catechol by both ortho- and meta-routes, and some strains possess a modified 3-oxoadipate pathway. Biotransformations catalyzed by rhodococci include steroid modification, enantioselective synthesis, and the transformation of nitriles to amides and acids. Tolerance of rhodococci to starvation, their frequent lack of catabolite repression, and their environmental persistence make them excellent candidates for bioremediation treatments. Some strains can produce poly(3-hydroxyalkanoate)s, others can accumulate cesium, and still others are the source of useful enzymes such as phenylalanine dehydrogenase and endoglycosidases. Other actual or potential applications of rhodococci include desulfurization of coal, bioleaching, use of their surfactants in enhancement of oil recovery and as industrial dispersants, and the construction of biosensors.

Biodegradation, Environmental↗

Charge calculations in molecular mechanics. IX. A general parameterisation of the scheme for saturated halogen, oxygen and nitrogen compounds.

The CHARGE2 program for the calculation of partial atomic charges has been amended to include bond parameters for a number of organic functional groups, including halogens, nitrogen and oxygen. These minor amendments to the original scheme produce dipole moments for the fluoro and chloro compounds which are in complete agreement with the observed values. The less complete data sets for the bromo and iodo compounds are also well reproduced, and the dipole moments of a variety of mixed halo compounds are now in better agreement with experiment than previously. The calculated dipole moments of the saturated nitrogen and oxygen compounds are now in much better agreement than in the original scheme, thus the revised parameterisation may be employed with confidence to predict the electrostatic energies of these compounds. Furthermore, the revised scheme now gives a precise proportionality between the charge on the proton in a CH group and the 1H chemical shift of the corresponding proton, allowing the general prediction, in principle, of 1H chemical shifts. In addition, attempts to include variable electronegativity in the alpha effect are described for fluoro compounds.

Chemistry, Organic↗

Halogenated phenols in water at forty Canadian potable water treatment facilities.

Samples of raw and treated water were collected once in each of 3 seasons at 40 potable water treatment plants across Canada and were analyzed for phenol and 33 halogenated phenolic compounds including chlorophenols, bromophenols, bromochlorophenols, and chloroguaiacols. Eighteen of the compounds were not found at any treatment plant; phenol and each of the remaining halogenated phenols were found in at least 1 sample. Pentachlorophenol was the only halogenated phenolic compound found in more than 20% of the raw water samples in the fall and winter samples at levels up to 53 ng/L with mean values of 1.9 and 2.8 ng/L, respectively. No halogenated phenols were detected in raw water summer samples. The halogenated phenols found most frequently in treated water samples were 4-chloro-, 2,4-dichloro-, 2,4,6-trichloro-, and bromodichlorophenols. Mean values were less than 15 ng/L and maximum values seldom exceeded 100 ng/L. Most of the positive values for the treated water samples were found at 8 of the 40 treatment plants but no correlations could be found between halogenated phenol levels and raw water type, treatment process, or chemical dosages.

Canada↗