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Development of quantitative structure-activity relationship (QSAR) models for predicting risk of exposure from carcinogens in animals.

Quantitative structure-activity relationship (QSAR) models capable of predicting acute toxicity and carcinogen potency of polychlorinated dibenzo-p-dioxin (PCDD), polychlorinated hydrocarbons, and chlorinated insecticides have been formulated. Median lethal dose (LD50) for PCDD-exposed mice correlated negatively with polarity and positively with (H acceptor x 2 chi), whereas LD50 for PCDD-exposed guinea pigs correlated with (H acceptor x density). Both (H acceptor x 2 chi) and (H acceptor x density) exhibited parabolic relationship with log P (partition coefficient). Carcinogenic potency, determined from order of magnitude (OM) values, correlated negatively with log P and positively with (length x width). Thus, a hydrophobic mechanism plays a key role in the lethal effects of PCDD in mice, whereas both hydrophobic and electronic mechanisms are involved in the lethal effects of PCDD in guinea pigs. However, the molecule's lipophilicity, length, and width may play important roles in the carcinogenic effects of chlorinated compounds.

Animals↗

Generation of nitrogen-chlorine oxidants by human phagocytes.

Human phagocytes can be triggered to generate large quantities of long-lived nitrogen-chlorine derivatives. This class of oxidants can be detected as early as 5 min after the addition of phorbol myristate acetate or opsonized zymosan particles. Unlike all other oxygen metabolites known to be generated by phagocytes, the nitrogen-chlorine compounds can be readily detected in cell supernatants 90 min after stimulation. The generation of these oxidants is linear with neutrophil concentration, favored at alkaline pH, and inhibited by supraphysiologic concentrations of iodide or bromide. The oxidants are hydrophilic in nature and have a half-life ranging from 5 h at 37 degrees C to greater than 100 h at 4 degrees C. Gel filtration chromatography of the accumulated nitrogen-chlorine derivatives revealed that the oxidants generated by neutrophils or monocytes are a complex mixture of products whose Mr range from 150-5,000. One-half of the nitrogen chlorine derivatives migrate as a single peak with an Mr of approximately 150. Amino acid analysis of this fraction identified the beta-amino acid, taurine, as the single nitrogenous compound present. Neutrophils triggered in the presence of serum albumin accumulated increased amounts of the nitrogen-chlorine derivatives while continuing to generate their endogenous low Mr oxidants. Quantitative analysis of the 36Cl incorporation revealed that the albumin molecule was chlorinated with the formation of both nitrogen-chlorine and carbon-chlorine bonds. We conclude that human phagocytes can chlorinate both endogenous and exogenous nitrogenous compounds at inflammatory sites to generate a heterogeneous mixture of nitrogen-chlorine derivatives. The ability of phagocytes to generate this class of long-lived oxidants whose hydrophilic characteristics restrict their localization to the extracellular space suggests that these species play an important role in modulating the inflammatory response.

Albumins↗

Fate of wood extractives in wastewater treatment plants at kraft pulp mills and mechanical pulp mills.

Extensive environmental effects of the forest industry led to implementation of activated sludge treatment of effluents in the 1980s. Although the existence of chlorinated compounds in the effluents has decreased, a discussion about the possible environmental effects of elemental-chlorine-free (ECF) and total-chlorine-free (TCF) bleached pulp mill effluents has arisen, and chronic effects on aquatic organisms have still been found. Recently, studies have mainly focussed on wood extractives and their role in the effects of effluents. Resin acids and unsaturated fatty acids are found to be toxic, and plant sterols are reported to have adverse endocrine effects on water organisms already at low concentrations. In this study, Finnish wastewater treatment plants of an ECF kraft pulp mill, a paper mill, and an integrated TCF kraft pulp and paper mill were sampled in order to ascertain how wastewater treatment plants, and especially activated sludge treatments, remove wood extractives. Concentrations of extractives in discharged wastewaters varied between 0.4 and 11 g/t kraft or mechanical pulp, and the concentrations decreased over 95% during the treatment processes. Of the wood extractives, 1.1-64% were adsorbed to biosludge and 35-99% were degraded or transformed to other forms during the activated sludge treatment. A major part of these compounds were discharged in particles (74-99%). The removal of extractives was efficient even in the effluent treatment plant, which was highly loaded during the sampling period.

Environmental Monitoring↗

Degradation of organochlorine compounds in spent sulfite bleach plant effluents by actinomycetes.

Actinomycetes isolated from different soil samples were tested for their abilities to utilize spent sulfite bleach effluents from a paper mill. Degradation and dechlorination of the chlorinated compounds in the effluents of the first two bleaching stages, i.e., chlorination stage [(C + D)red.] and alkaline extraction stage (E1O), were monitored by determining total organic carbon (TOC) and activated-carbon-adsorbable organic-bound halogen (AOX). The isolates showed increased degradation rates after repeated incubations in the effluent-containing medium. Separation of the culture supernatants by ultrafiltration into three fractions of different molecular weights revealed substantial AOX and TOC reductions in the low-molecular-weight fraction. The AOX values of the higher-molecular-weight fractions were also reduced. Extracellular peroxidase and cell wall-bound catalase activities were produced during growth of the microorganisms on bleach effluents.

Actinomycetales↗

Adsorption of volatile organic compounds onto carbon nanotubes, carbon nanofibers, and high-surface-area graphites.

The adsorption of different alkanes (linear and cyclic), aromatics, and chlorohydrocarbons onto different nonmicroporous carbons--multiwalled carbon nanotubes (CNTs), carbon nanofibers (CNFs), and high-surface-area graphites (HSAGs)--is studied in this work by inverse gas chromatography (IGC). Capacity of adsorption was derived from the isotherms of adsorption, whereas thermodynamic properties (enthalpy of adsorption, surface free energy characteristics) have been determined from chromatographic retention data. HSAGs present the highest adsorption capacity, followed by CNTs and CNFs (although CNTs present an intermediate surface area between the two HSAG studied). Among the different adsorbates tested, benzene exhibits the highest adsorption capacity, and the same trend is observed in the enthalpy of adsorption. From surface free energy data, enthalpies of adsorption of polar compounds were divided into dispersive and specific contributions. The interactions of cyclic (benzene and cyclohexane) and chlorinated compounds (trichloroethylene, tetrachloroethylene, and chloroform) with the surfaces are mainly dispersive over all the carbons tested, CNTs being the material with the highest dispersive contribution, as was deduced also from the entropy parameter. Adsorption parameters were correlated with morphological and chemical properties of the materials.

Journal Article↗

Behavior of hydrogen peroxide in electrolyzed anode water.

Oxygen electrodes and spectrophotometric analysis have been used to evaluate the contribution of H2O2, in addition to available chlorine, to the high redox potential of electrolyzed anode water (EAW) with potassium chloride as an electrolyte. H2O2 was added externally to EAW, and the reaction between H2O2 and the available chlorine in the water was examined. EAW has a low pH (2.5), a high concentration of dissolved oxygen, and extremely high redox potentials (19 mg/l and 1,319 mV) when the available chlorine is at the concentration of about 580 microM. The addition of H2O2 to EAW led to H2O2 decomposition, and the amount of oxygen produced was equivalent to the amount of available chlorine. Oxygen production was reduced by ascorbic acid, and completely inhibited by 600 microM ascorbate. The rate of oxygen production was much affected by pH, and was slowest at or near pH 5.0. Rates were particularly high in alkaline solution. Absorbance at 235 nm (pH 3.0 and 5.0) and 292 nm (pH 10.0) decreased when H2O2 was added to the EAW at these pHs, and the extent of decrease was similar pH dependency to that of the oxygen production rate. Oxygen was not produced after H2O2 was added to EAW at pH 2.6 when available chlorine was absent, but oxygen was produced after potassium hypochlorite was added to such EAW. The oxygen production rates in EAW without available chlorine at pH 5.0 and 2.0, pH adjustment with KOH and HCl, respectively, were faster than the rate at pH 2.6, and fastest at pH 2.0. These results suggest that H2O2 or hydroxyl radicals derived from Fenton's reaction did not contribute to the high redox potential of EAW prepared with chlorine compounds as an electrolyte, so that the decomposition of H2O2 occurred rapidly with the reactions of chlorine and hypochlorite ions in EAW.

Ascorbic Acid↗

Environmental health in the east Baltic region--pesticides and persistent organic compounds.

Exposure to, and the potential effects of, pesticides and persistent organic pollutants in the East Baltic region are reviewed. Exposure of the average population to chlorinated compounds seems lower than in most of western Europe, and current pesticide use is very low. However, due to infrastructure failures and poor management controls, industrial hot spots and inadequate storage sites exist that cause high risks to small population fractions. The low exposure of the general population is indicated by low concentrations of polychlorinated dibenzo-p-dioxins, dibenzofurans and biphenyls in milk fat. Chlorophenol concentrations are also generally lower than in Scandinavia. Some organic pesticides have been found at higher concentrations in Baltic countries and the St. Petersburg area than in Norway, but the range is roughly similar to that in central Europe. Thus the overall risk caused by pesticide residues and persistent organic compounds in the Baltic countries and northwestern Russia is low, but local sites of concern exist.

Baltic States↗

PCDD/F TEQ indicators and their mechanistic implications.

Stack gas samples from two incinerator facilities with different operating conditions were investigated to understand how indicators of toxic equivalency (TEQ) from among the 210 polychlorinated dibenzo-p-dioxin/furan (PCDD/F) isomers varied. This effort was motivated by the need to find more easily monitored indicator compound(s) of TEQ and to reconcile the varying indicator compounds reported in the literature. The measured isomer patterns were compared with those expected from known formation mechanisms to identify the dominant mechanism(s) and explain why certain compounds are relevant TEQ indicators. Despite differences in the facility types and operating conditions, a common pattern was found for the highly chlorinated (4Cl and higher) PCDDs/Fs. A combination of chlorination/dechlorination reactions as the dominant formation mechanism for PCDF was consistent with the observed isomer patterns, whereas condensation reactions of phenolic precursors appeared to be responsible for PCDD formation. PCDF isomers, ratherthan the PCDD isomers, were more closely related to the TEQ measure, likely because the chlorination mechanism favors 2,3,7,8-Cl-substitution more than the phenol condensation mechanism. Unlike highly chlorinated PCDD/F isomer patterns, less chlorinated PCDD/F patterns (especially, mono- and di-CDF) were sensitive to operating conditions and facility type. Competing formation mechanisms were inferred from the variation of observed isomer distribution patterns; this sensitivity resulted in relatively low correlations of these isomers with PCDD/F TEQ values. This suggests that any use of the low-chlorinated compounds as TEQ indicators for online monitoring processes are likely best suited for plant-specific, rather than universal, applications. In addition to many of the highly chlorinated (penta-CDF, hexa-, and heptaCDD/F) isomers being identified as strong TEQ indicators, 1 of 12 (8%), 5 of 17 (29%), and 5 of 28 (18%) of the separable tri-CDD, tri-CDF, and tetra-CDF isomers, respectively, were identified as strong (R2 > 0.7) TEQ indicators in both incinerators.

Air Pollutants↗

An equilibrium analysis of some chlorinated hydrocarbons in stoichiometric to fuel-rich post-flame combustion environments.

The equilibrium composition of product gases from the combustion of chlorinated hydrocarbons (CHC) has been studied for varying ratios of C, H, Cl, and O under stoichiometric to fuel-rich conditions. An interactive, PC-compatible FORTRAN program, STANJAN, was utilized in conjunction with thermochemical data sources to calculate equilibrium compositions of gas mixtures as a function of temperature. The predicted results, when judiciously interpreted, assist in the understanding of the potential for formation of residual organic substance emissions (ROSEs) in post-flame environments of an incinerator. Arguments are presented for the potential formation of chlorinated species, which are stable at ambient temperature, if locally fuel-rich mixtures penetrate into the lower temperature zones of an incinerator. ROSEs that have been observed in field tests of incinerators burning chlorinated compounds are predicted to form under the fuel-rich condition. Furthermore, when the equivalence ratio is greater than unity by even a slight amount, the degree of chlorination of product gases increases markedly when the Cl/H ratio also exceeds unity. In that case, time, temperature, turbulence and an overall fuel-lean stoichiometry may not be sufficient to guarantee elimination of measurable levels of chlorinated products. Possible implications of the equilibrium calculations are discussed. Further systematic studies with additional CHCs, nitrogen-, sulfur-, and heavy metal-bearing compounds are recommended as well as continued efforts to carry out kinetic studies.

Air Pollutants, Occupational↗

In vivo detection of genotoxicity in waste water from a wheat and rye straw paper pulp factory.

The genotoxicity of waste water from a wheat and rye straw paper pulp mill was investigated by in vivo genotoxicity tests using micronuclei and sister chromatid exchange as endpoints. Micronuclei were studied in mussels (Mytilus edulis) and sister chromatid exchange in fish (Nothobranchius rachowi). The paper mill uses chlorine dioxide for bleaching, and the bleaching effluent as well as the combined effluent, i.e. the mixture of all waste water streams, were both tested. Both effluents induced micronuclei and sister chromatid exchanges, although the presence of toxic substances could mask the expression of genotoxicity in some cases for both test systems. The study revealed that genotoxins are produced in the chlorine dioxide bleaching process as well as in the pulping process, indicating also genotoxic activity of non-chlorinated compounds. In contrast to previous studies in which mutagenicity was determined with bacterial assays, genotoxins were only associated with chlorinated organics from bleaching with chlorine and failed in detecting genotoxins in chlorine dioxide bleaching effluents. Aquatic in vivo genotoxicity tests are sensitive and efficient systems and seem to be a promising tool in effluent testing.

Animals↗

Engineering dioxygenases for efficient degradation of environmental pollutants.

Dioxygenases have recently been engineered to improve their capabilities for environmental pollutant degradation. The techniques used to achieve this include in vitro DNA shuffling and subunit or domain exchanges between dioxygenases of different bacterial origins. Such evolved enzymes acquire novel and enhanced degradation capabilities of xenobiotic compounds, such as polychlorinated biphenyls, trichloroethylene and a variety of aromatic compounds. Hybrid strains in which the evolved genes are integrated into the chromosomal operons exhibit efficient degradation of xenobiotic chlorinated compounds.

Amino Acid Sequence↗

Bactericidal effect of chlorine on motile Aeromonas spp. in drinking water supplies and influence of temperature on disinfection efficacy.

The susceptibility of toxigenic Aeromonas spp. to free chlorine in drinking water supplies, and the influence of environmental temperature on the bactericidal activity of the oxidant, were evaluated. The results showed inactivation curves characterized by an initial phase of rapid reduction of viable cells followed by a slow inactivation of bacteria. The effect of the chlorine compound was markedly influenced by water temperature. At a summer water temperature (20 degrees C), the efficacy of the chlorine concentrations tested was found to be two to three times lower compared to that found at a winter temperature (5 degrees C). Resistance was moderately, but significantly, greater in Aer. hydrophila vs Aer. caviae and Aer. sobria, but all Aeromonas spp. were more susceptible than Escherichia coli. Selective pressure with free chlorine did not produce Aeromonas cells with higher levels of chlorine resistance.

Aeromonas↗

Commercial polyurethanes: the potential influence of auxiliary chemicals on the biodegradation process.

This investigation elucidates some aspects of auxiliary chemicals on the biodegradation of two commercial polyurethanes (Pellethane and Corethane). The materials were incubated for 28 days with cholesterol esterase and/or with phosphatidylcholine. Extraction studies were carried out on the two materials, using different solvents, chosen on the basis of solvent polarity. FT-IR spectra for the extracted materials indicated the presence of poly(methylene)n oxide moities, silicone oil, bis-ethylene-stearamide, aromatic moities, and alkyd-urea compounds in Pellethane. Corethane materials were shown to contain some fatty acids, hydrocarbon waxes, ester-based species, and chlorinated compounds. Analysis of incubation solutions by high performance liquid chromatography failed to isolate methylene dianiline (MDA) or any of its derivatives from the various polymer incubation solutions. However, a methanol extract of Corethane samples that were incubated for 28 days in cholesterol esterase did show the presence of MDA. The absence of MDA in the Pellethane methanol extracted samples may reflect the differences in surface additives found for this material versus the Corethane. FT-IR/ATR analysis of polymer surfaces exposed to cholesterol esterase/phospholipids mixture showed that there was an increase in the uptake of phospholipids over samples that were incubated in phospholipid dispersion alone. The results of this study show that some of the auxiliary chemicals found in commercial polyurethanes may hinder the specific release of hydrolytic degradation products and delay polymer degradation. However, it should be recognized that the surface layer containing these compounds is susceptible to change following the interaction between the polyurethane-based devices and elements of the host environment (i.e. lipids, enzymes, etc.). Hence, recognition and identification of these changes will ultimately be important in assessing a commercial polymer's blood compatibility characteristics.

Biodegradation, Environmental↗

[Chlorine coatings on skin surfaces. II. Parameters influencing the coating strength].

Although active chlorine compounds have been used for more than 140 years (Semmelweis, 1848) as a skin disinfectant the phenomenon of the "chlorine covers" not earlier than 1988 has been described for the first time (Hyg. + Med. 13 (1988) 157). It deals with a chemical alteration of the uppermost skin layer which comes apparent in an oxydizing action against aqueous iodide. Its origin is chlorine covalently bound in the form of N-Cl functions to the protein matrix of the horny skin. Since the chlorine covers exhibit a persistant disinfecting activity which might be important for practice, the factors influencing their strength have been established. The most important are: the kind of the chlorine system, the concentration (oxydation capacity), pH, temperature and the volume of the used solution, the time of action, the application technique and the state of the skin. Variations of the latter can be observed at different skin areas of one and the same person as well as at the same areas of different persons, and result in differences of the cover strength up to 100%. The stability on dry skin is very good, showing a decomposition rate of approximately 1.2% per hour. However on skin surfaces moistened by sweat (e.g. hands covered by surgeons gloves) the chlorine cover is disingrated much more faster (decomposition rate: 40-50% per hour). Washing with soap as well as the action of alcohols cause virtually no decrease in the cover strength, while wetting by solutions of reducing agents (e.g. thiosulfate, cysteine, iodide) provokes a fast decomposition suitable for removing the chlorine covers.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohols↗

Organochlorine compounds in relation to breast cancer, endometrial cancer, and endometriosis: an assessment of the biological and epidemiological evidence.

There is an increasing public and scientific concern that certain chlorinated compounds, recognized as environmental pollutants, may cause estrogen-related neoplastic disease in humans. The main hypothesis has been that certain organochlorines, through their estrogenic actions, might cause breast cancer. From experimental studies, both in vitro and in vivo, there is evidence that certain organochlorine compounds may cause estrogenic effects, whereas others may cause antiestrogenic effects. In limited studies, some of these compounds in high doses have also been shown to increase and reduce the frequency of estrogen-related tumors in animals. The epidemiological findings regarding the association between organochlorines and breast cancer are inconclusive. However, the largest and best designed study has been interpreted as negative with respect to DDT and polychlorinated biphenyls (PCB) in relation to breast cancer. Associations between organochlorine exposure and endometrial cancer or endometriosis have even more limited empirical basis. The hypothesis that human exposure to environmental levels or organochlorines would favor an estrogenic overactivity leading to an increase in estrogen-dependent formation of mammary or endometrial tumors is not supported by the existing in vitro, animal and epidemiological evidence. It can, however, not be conclusively rejected on the basis of available data.

Animals↗

Induction of popliteal lymph node enlargement and antibody production in the mouse by pyridylallylamines related to zimeldine.

The role of the para-brominated phenyl ring of the allylamine antidepressant drug, zimeldine, in its immunomodulating activity was studied by comparing local lymph node responses of mice to analogues with various phenyl ring substituents. The compounds (1.0 mg) were injected into the hind footpad and weight and cell number of the popliteal lymph node (PLN) and antibody production by PLN cells were determined 7 days later. Zimeldine and the para-trimethylsilylated and ortho-para-chlorinated compounds induced a marked PLN weight gain in C57BL/6 mice. The para-chlorinated and meta-brominated analogues were significantly less effective, while the para-fluorinated and the unsubstituted analogue failed to trigger PLN weight gain. The same range of potency of the compounds was seen when increases of PLN cell number in BALB/c mice and increases of IgM production by a fixed number of BALB/c PLN cells were determined. The IgG production on a per cell basis was not increased by the fluorinated and the unsubstituted compounds, while the remaining compounds stimulated the IgG production to a similar extent. Plots of the lipophilicity of the para-substituted compounds against their ability to induce PLN weight and cell gain showed a fair correlation, but induction of antibody formation tended to be counteracted at too high lipophilicity. No correlation between pharmacologic and immunologic activity of the compounds could be found. Data indicate that lipophilicity grossly favours PLN enlargement, but the divergent responses to the equilipophilic 3- and 4-brominated compounds, suggest conformational restraints as well.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Adsorption characterisation of different volatile organic compounds over alumina, zeolites and activated carbon using inverse gas chromatography.

Adsorption parameters (enthalpy of adsorption, free energy of adsorption) of several alkanes, cyclic hydrocarbons, aromatic hydrocarbons and chlorinated compounds on different adsorbents (alumina, zeolites 13X and 5 A, and activated carbon) were determined by inverse gas chromatography. Dispersive surface energy interaction and specific interaction parameters were determined for each solute-adsorbent system. It was found that mesoporous alumina presents lower enthalpy of adsorption than the microporous materials. Furthermore, zeolite 13X, which has wider pores than zeolite 5 A, exhibits a higher adsorption capacity.

Adsorption↗

Literature review--efficacy of various disinfectants against Legionella in water systems.

There have been reported outbreaks of Legionnaires' disease at hospitals and industrial facilities, which prompted the development of various preventive measures. For example, Ford has been developing and implementing such a measure at its facilities worldwide to provide technical guidance for controlling Legionella in water systems. One of the key issues for implementing the measure is the selection of a disinfectant(s) and optimum conditions for its use. Therefore, available publications on various disinfectants and disinfection processes used for the inactivation of Legionella bacteria were reviewed. Two disinfection methods were reviewed: chemical and thermal. For chemical methods, disinfectants used were metal ions (copper and silver), oxidizing agents (halogen containing compounds [chlorine, bromine, iodine, chlorine dioxide, chloramines, and halogenated hydantoins], ozone, and hydrogen peroxide), non-oxidizing agents (heterocyclic ketones, guanidines, thiocarbamates, aldehydes, amines, thiocyanates, organo-tin compounds, halogenated amides, and halogenated glycols), and UV light. In general, oxidizing disinfectants were found to be more effective than non-oxidizing ones. Among oxidizing agents, chlorine is known to be effective and widely used. Among non-oxidizing agents, 2,2-dibromo-3-nitropropionamide appears to be the most effective followed by glutaraldehyde. Isothiazolin (known as Kathon), polyhexamethylene biguanide, and 2-bromo-2-nitropropionamide (known as Bronopol) were found to be less effective than glutaraldehyde. Thermal disinfection is effective at > 60 degrees C (140 degrees F).

Developing Countries↗