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In vivo studies on halogen compound interactions. II. Effects of carbon tetrachloride plus 1,2-dibromoethane on relative liver weight and hepatic steatosis.

A mixture of carbon tetrachloride (CCl4) and 1,2-dibromoethane (DBE) results in a significant increase in relative liver weight (RLW) when compared with the effect of each substance individually. At the same time, the liver triglyceride levels of rats treated with the mixture are lower than in those treated with CCl4 alone. This increase in RLW is not caused by simple tissue oedema. Lipoprotein secretion and the concentration of circulating non esterified fatty acids (NEFA) are not involved in the DBE-induced reduction of steatosis provoked by CCl4. The synthesis of triglycerides is significantly depressed in animals treated with the mixture. These findings provide further evidence of the previously observed enhancement of liver toxicity caused by the simultaneous presence of both agents, since the apparent protection against steatosis is due to greater damage to the liver cell, which is no longer able to counter the steatogenic action of CCl4 through a sufficient synthesis of triglycerides.

Animals↗

A novel halogenated compound possessing antibiotic and cytotoxic activities isolated from the fungus Resinicium pinicola (J. Erikss.) Erikss. & Hjortst.

Pinicoloform, a novel unbranched acyclic compound containing a trichloromethyl group, has been isolated from extracts of the mycelia of the Basidiomycete Resinicium pinicola. It was isolated because of its ability to induce morphological and physiological differentiation of mammalian cells, although it also exhibits antibiotic and cytotoxic activities. The structure of pinicoloform was determined by spectroscopic methods.

Animals↗

[Flame retardants--use and hazards for human].

Flame retardants (FRs) are chemicals which added to materials during or after manufacture, inhibit or even suppress the combustion process due to their thermal stability. Large quantities of FRs are added to the plastic material (resins) in variety of electrical and electronic appliances including television and computer casing. The other uses of these compounds include production of building materials, upholstered furniture, textiles, wall covering, carpets, hydraulic fluids as well as vehicles and aircraft. Taking into account the chemical structure, there are five main groups of FRs: brominated, chlorinated, phosphorous-containing, nitrogen-containing (i.e. melamines) and inorganic compounds. Halogenated compounds, especially polybrominated diphenyl ethers (PBDEs), a class of brominated flame retardants, due to their lipophilic characteristics and persistence have become ubiquitous environmental contaminants. There are indications that PBDEs may affect hormone function acting as endocrine disruption and may be toxic for developing brain. These compounds have been associated with non-Hodgkin's lymphoma in humans, a variety of cancers in rodents and disruption of thyroid hormones balance. Similarly to other persistent halogenated compounds they are also able to affect the xenobiotic metabolizing enzymes activity. PBDEs are now found as residues in sediments, wildlife and human (milk, serum adipose tissue) samples. The predominant congeners in environmental samples, including human specimens are two congeners: 47 and 99. Currently, the estimated daily intake of PBDEs by adult humans is equal 51 ng x day-1 while by breast-fed infants equals 110 ng x day-1.

Carcinogens↗

The use of stable isotopes to identify reactive metabolites and target macromolecules associated with toxicities of halogenated hydrocarbon compounds.

1. Halogenated compounds, such as the inhalation anaesthetics, halothane and enflurane, and the chemicals chloroform, carbon tetrachloride, and bromotrichloromethane can cause hepatotoxicity, nephrotoxicity, and inactivation of cytochromes P-450. Each of these toxicities is mediated by reactive metabolites. 2. Stable isotopes of hydrogen, carbon, chlorine and oxygen have been used in conjunction with mass spectrometry and n.m.r. spectrometry to identify the structures of these metabolites, to elucidate the mechanisms of their formation, and to characterize the structures of their macromolecular adducts. 3. In a number of cases, oxidative pathways of metabolism to toxic metabolites have been defined by kinetic deuterium isotope effects. 4. Recently, we have found that the trichloromethyl radical metabolite of bromotrichloromethane can activate myoglobin by causing the covalent cross-linking of haem to protein. The structure of a haem-myoglobin adduct has been defined by the use of stable isotope studies.

Animals↗

Radiocarbon content of synthetic and natural semi-volatile halogenated organic compounds.

Some halogenated organic compounds, such as polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and polybrominated diphenyl ethers (PBDEs), have been suggested to have natural sources but separating these compounds from their commercially synthesized counterparts is difficult. Molecular-level 14C analysis may be beneficial since most synthetic compounds are manufactured from petrochemicals (14C-free) and natural compounds should have "modern" or "contemporary" 14C levels. As a baseline study, we measured, for the first time, the 14C abundance in commercial PCB and PBDE mixtures, a number of organochlorine pesticides, as well as one natural product 2-(3',5'-dibromo-2'-methoxyphenoxy)-3,5-dibromoanisole. The latter compound was isolated from a marine sponge and is similar in structure to a PBDE. All of the synthetic compounds were 14C-free except for the pesticide toxaphene. which had a modern 14C abundance, as did the brominated natural compound. The result for toxaphene was not surprising since it was commercially synthesized by the chlorination of camphene derived from pine trees. These results suggest that measuring the 14C content of halogenated organic compounds may be quite useful in establishing whether organic compounds encountered in the environment have natural or synthetic origins (or both) provided that any synthetic counterparts derive from petrochemical feedstock.

Animals↗

Current use of skin and wound cleansers and antiseptics.

Out of the tumult of a turbulent, eight-century-long background of surgical skin and wound cleansing methods has come a set of basic principles that serve as performance specifications for new developments. Alcohol remains the superior skin antiseptic. Its characteristic rapid-drying effect and consequent loss of bactericidal action can be overcome by maintaining wetness or by admixture with emollients or longer-acting antiseptics. Today's combinations of cleaners, alcohol, and either iodophores or chlorhexidine have emerged from previous eras characterized by the use of metallic compounds, halogen compounds, and tincture of iodine. Published guidelines are important but must be looked upon as current consensus rather than standard practice.

Anti-Infective Agents, Local↗

Cluster analysis of acrylates to guide sampling for toxicity testing.

A set of 143 acrylates drawn from the TSCA inventory have been investigated for structurally defined clusters of compounds to simplify sampling for future toxicity screening. Each acrylate was represented by eight descriptors calculated from the molecular structure. Several standard clustering methods have been used to find five natural clusters of compounds. These five clusters are largely populated by compounds with similar chemical attributes with separate clusters formed for compounds with high absolute partial atomic charges, hydrophobic compounds, small compounds, halogenated compounds, and large or oligomeric compounds.

Acrylates↗

[Classification of harmful gases].

The classification of harmful gases may be envisaged in various ways according to the criteria considered. The two aspects adopted here concern chemical and toxicological classifications. Chemical classification is in general based upon the nature of the elements constituting the gases, e.g. carbon, nitrogen, sulphur, phosphorus, halogen compounds and halogenated compounds, etc. Toxicological classification is envisaged on the basis of the concepts of toxicity itself. It may then be used to establish the scale of its degree based upon two principal factors: concentration and duration of exposure. However, certain observations suggest complex intoxication phenomena related to an overall number of factors which are generally considered in isolation.

Animals↗

Degradation of halogenated aliphatic compounds: the role of adaptation.

A limited number of halogenated aliphatic compounds can serve as a growth substrate for aerobic microorganisms. Such cultures have (specifically) developed a variety of enzyme systems to degrade these compounds. Dehalogenations are of critical importance. Various heavily chlorinated compounds are not easily biodegraded, although there are no obvious biochemical or thermodynamic reasons why microorganisms should not be able to grow with any halogenated compound. The very diversity of catabolic enzymes present in cultures that degrade halogenated aliphatics and the occurrence of molecular mechanisms for genetic adaptation serve as good starting points for the evolution of catabolic pathways for compounds that are currently still resistant to biodegradation.

Adaptation, Physiological↗

Quantitative structure-activity relationships for toxicity and genotoxicity of halogenated aliphatic compounds: wing spot test of Drosophila melanogaster.

Halogenated aliphatic compounds were evaluated for toxic and genotoxic effects in the somatic mutation and recombination test employing Drosophila melanogaster. The tested chemicals included chlorinated, brominated and iodinated; mono-, di- and tri-substituted; saturated and unsaturated alkanes: 1,2-dibromoethane, 1-bromo-2-chloroethane, 1-iodopropane, 2,3-dichloropropene, 3-bromo-1-propene, epibromohydrin, 2-iodobutane, 3-chloro-2-methylpropene, 1,2,3-trichloropropane, 1,2-dichloroethane, 1,2-dichlorobutane, 1-chloro-2-methylpropane, 1,3-dichloropropane, 1,2-dichloropropane, 2-chloroethymethylether, 1-bromo-2-methylpropane and 1-chloropentane. N-methyl-N-nitrosourea served as the positive and distilled water as the negative control. The set of chemicals for the toxicological testing was selected by the use of statistical experiment design. Group of unsaturated aliphatic hydrocarbons were generally more toxic than saturated analogues. The genotoxic effect was observed with 14 compounds in the wing spot test, while 3 substances did not show any genotoxicity by using the wing spot test at 50% lethal concentration. The highest number of wing spots was observed in genotoxicity assay with 1-bromo-2-chloroethane, 1,2-dichloroethane, 1,2-dibromoethane and 1-iodopropane. Nucleophilic superdelocalizability calculated by quantum mechanics appears to be a good parameter for prediction of both toxicity and genotoxicity effects of halogenated aliphatic compounds.

Animals↗

Reductive dechlorination of polychlorinated biphenyls as affected by natural halogenated aromatic compounds.

We investigated the effects of halogenated aromatic compounds (HACs) including naturally occurring ones (L-thyroxine, 3-chloro-L-tyrosine, 5-chloroindole, 2-chlorophenol, 4-chlorophenol and chlorobenzene) on polychlorinated biphenyl (PCB) dechlorination in sediment cultures. A PCB-dechlorinating enrichment culture of sediment microorganisms from the St. Lawrence River was used as an initial inoculum. When the culture was inoculated into Aroclor 1248 sediments amended with each of the six HACs, the extent of dechlorination was not enhanced by amendment with HACs. The dechlorination patterns in the HAC-amended sediments were nearly identical to that of the HAC-free sediments except the 3-chloro-L-tyrosine-amended ones where no dechlorination activity was observed. When these sediment cultures were transferred into fresh sediments with the same HACs, the dechlorination specificities remained the same as those of the initial inoculations. Thus, in the present study, the substrate range of the highly selected enrichment culture could not be broadened by the HACs. It appears that HACs affect PCB dechlorination mainly through population selection rather than enzyme induction of single population.

Aroclors↗

Boiling points of halogenated organic compounds.

The normal boiling points of a number of halogenated organic compounds have been compiled from experimental measurements over three decades. Some of these chemicals have not been reported in the literature. The substances listed are halogenated aliphatic hydrocarbons, halogenated aliphatic ethers, halogenated ring (cyclic) hydrocarbons and other related compounds.

Halogens↗

Evaluation of modulators and electron-capture detectors for comprehensive two-dimensional GC of halogenated organic compounds.

Different cryogenic and a heated GC x GC modulator(s) were evaluated and compared for the analysis of high-boiling halogenated compounds. The cryogenic modulators investigated were: (i) the longitudinally modulated cryogenic system; (ii) the liquid-nitrogen-cooled jet modulator (KT2001); (iii) a dual-jet CO2 modulator (made in-house); (iv) a semi-rotating cryogenic modulator (made in-house) and (v) a CO2 loop modulator (KT2003); the heated modulator was the slotted heater system (sweeper). Each modulator was optimised with respect to analyte peak widths at half height in the second-dimension. n-Alkanes, chlorinated alkanes, polychlorinated biphenyls (PCBs) and fluorinated polycyclic aromatic hydrocarbons (F-PAHs) were used as test analytes. The flow rate of the coolant was found to be an important parameter, i.e. the flow rate of the gaseous nitrogen in the KT2001, and of the liquid CO2 in the other cryogenic modulators. For the slotted heater the stroke velocity and pause time were important parameters. This modulator had a limited application range in terms of temperature due to a necessary 100 degrees C difference between sweeper and oven temperature. All cryogenic modulators were found to be suitable for the GC x GC analysis of high-boiling compounds, but the CO2 modulators are to be preferred to the KT2001 due to a wider application range and slightly narrower peaks. As regards the performance of three commercially available electron-capture detectors (ECDs), the aim was to obtain narrow peak widths in GC x GC, i.e. to avoid band broadening caused by the cell volume. The most important parameters were the flow rate of the make-up gas and the detector temperature which both should be as high as possible. Comparison of analyte peak widths obtained with ECD mode and flame ionisation detection (FID) showed that all ECDs exhibited band broadening compared to the FID. The narrowest peaks were obtained with the Agilent micro-ECD, which has a cell volume of only 150 microl.

Chromatography, Gas↗