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Sterol-content lowering action of o-chlorobenzylchloride in yeast.

o-Chlorobenzylchloride, a simple aromatic halogen compound, was found to inhibit the growth of Saccharomyces cerevisiae and to lower the contents of sterols and fatty acids. The growth inhibition was considerably alleviated by the presence of sterols such as ergosterol and cholesterol and of unsaturated fatty acids such as oleate and linolenate. Inspection of effect of the inhibitor on the electron transport system related to the biosyntheses of these compounds revealed that the cytochrome contents and some enzyme activities in the system of the inhibited cells were much lower than those of the control cells. The features of the inhibition were similar to those of inhibition for other organisms by the hypocholesterolemic compounds such as triparanol and benzmalecene.

Benzyl Compounds↗

A limited epizootic of neuroblastoma in coho salmon reared in chlorinated-dechlorinated water.

During the 1976-77 brood year, approximately 12 cases of neuroblastoma were observed in a captive group of 100,000 fingerling coho salmon (Oncorhynchus kisutch) reared in a commercial hatchery. The tumors were large, occurring in the skeletal muscle near the dorsal fin causing conspicuous bulging of the overlying integument. Tumors examined from 3 fish each consisted of neuroblasts in trabecular patterns interspersed by glial fibrillar material and linear cavities resembling central neural canals lined by ependyma-like cells. Ganglion-like cells also were apparent morphologically and by special stain. Cancer of the tumor was characterized by an abundance of mitotic figures with occasional abnormal divisions, local invasion of normal tissues, and potentially metastatic tumor cell aggregates in organ vasculature. The etiology of this tumor may have been related to mutagenic-carcinogenic halogenated compounds possibly formed in the hatchery water supply during continuous chlorination of incoming river water.

Animals↗

Impairment of erythropoiesis in rats exposed to environmental pollutants.

The extent to which halogen compounds interfere with erythropoiesis is still unclear. This paper reports an evaluation of the effect of repeated exposure to carbon tetrachloride (CCl4) in air on red blood cell (RBC) creatine concentration. Creatine is neither synthetised nor metabolised in circulating RBC and decreases over the lifespan of red cells. It can thus be taken as a reliable indicator of mean RBC age, and hence of cell viability and bone marrow efficiency. Following inducement of hemolysis with phenylhydrazine (PHH) to stimulate erythropoiesis, creatine levels rose in the controls. This increase was significantly less in the CCl4-treated animals. It is not yet certain whether this inhibition reflects impaired marrow efficiency, enhanced RBC destruction in the marrow, or block of the release of mature RBC. The fact that such inhibition takes place, however, is of importance as a predictive factor in environmental toxicology, since it appears before changes in other blood parameters or signs of liver toxicity are observed.

Animals↗

Modified method for electron capture gas-liquid chromatographic determination of hexestrol residues in bovine tissues.

A gas-liquid chromatographic (GLC) method with electron capture detection was developed for determining hexestrol residues based on a GLC method for diethylstilbestrol residues. The extraction and purification procedures were based on a published procedure. Pentafluoropropionic (PFP) and heptafluorobutyric (HFB) anhydrides and other halogenated compounds were compared as acylation reagents. PFP anhydride was selected because it provided reproducible GLC responses. Of the 3 column packing materials tested, OV-17, OV-210, and QF-1, OV-17 was the most stable under the GLC conditions used. A pH 10.5--10.6 in the purification step gave higher recoveries than pH 10.3 or pH 10.8 and was selected for use. The method is suitable for determining residues of 0.5 ppb. The limit of sensitivity ranges from 0.1 to 0.2 ppb.

Animals↗

Anesthetics produce subunit-selective actions on glutamate receptors.

We assessed the involvement of specific glutamate receptors in the action of anesthetics. In addition to the clinical anesthetics enflurane, isoflurane and halothane, we tested novel halogenated compounds, which are anesthetic or nonanesthetic in vivo, on glutamate receptor (GluR) subunits. these volatile compounds as well as pentobarbital and phenobarbital were tested on kainate-induced currents in Xenopus oocytes expressing GluR1, GluR3, GluR2+3 or GluR6 subunits. The anesthetic 1-chloro-1,2,2-triflurocyclobutane (F3) weakly inhibited kainate responses in oocytes expressing GluR3 receptors but not oocytes expressing GluR1 or GluR2+3 receptors. Surprisingly, F3 potentiated kainate responses in oocytes expressing the kainate-selective receptor GluR6. The nonanesthetics 2,3-chlorooctafluorobutane (F8) and 1,2-dichlorohexafluorocyclobutane (F6) did not affect GluR3 or GluR6 kainate responses. Isoflurane weakly inhibited although enflurane and halothane modestly inhibited kainate responses in oocytes expressing GluR1, GluR3 or GluR2+3 receptors. As with F3, isoflurane, enflurane and halothane potentiated kainate-induced currents of GluR6 receptors. The respective inhibitory and potentiating effects of halothane on GluR3 and GluR6 receptors were enhanced by increasing duration of halothane exposure. In contrast to the opposing action of volatile anesthetics, pentobarbital and phenobarbital inhibited GluR3 and GluR6 kainate responses and had a much greater effect on GluR6 receptors. These results provide novel evidence that anesthetics produce selective actions on glutamate receptors, suggesting that subunit composition may determine the role of glutamate receptors in anesthesia.

Anesthetics↗

Inhibition of 5-hydroxytryptamine type 2A receptor-induced currents by n-alcohols and anesthetics.

5-Hydroxytryptamine type 2A receptors (5-HT2A) are G protein-coupled receptors that increase intracellular Ca2+ concentrations via activation of phospholipase C-beta and elevation of myo-inositol-1,4,5-triphosphate levels. In the central nervous system, these receptors are involved in regulating sleep and alertness. We now report that ethanol inhibited (IC50 = 41 mM) 5-HT2A receptor-induced Ca2+-dependent Cl- currents in Xenopus laevis oocytes. Pharmacologically relevant concentrations of other n-alcohols (propanol to octanol) also inhibited 5-HT responses; however, longer-chain alcohols (decanol, undecanol and dodecanol) had little or no effect. The protein kinase C inhibitor GF109203X and the nonspecific protein kinase inhibitor staurosporine abolished the inhibitory effects of ethanol and octanol on 5-HT2A receptors. GF109203X enhanced 5-HT2A receptor function when administered alone. In addition, the volatile anesthetics halothane and 1-chloro-1,2,2-trifluorocyclobutane decreased 5-HT2A responses in a concentration-dependent manner. The inhibitory effects of the volatile anesthetics were also attenuated in oocytes treated with GF109203X. The intravenous anesthetics propofol, ketamine, pentobarbital and etomidate did not affect 5-HT2A receptor function. The modulation of 5-HT2A receptor-dependent current was also investigated using two novel halogenated compounds that do not produce anesthesia. The nonanesthetic compound 2,3-chloro-octafluorobutane had no effects on 5-HT-induced currents; however, the nonanesthetic compound 1,2-dichlorohexafluorocyclobutane had an inhibitory effect at lower concentrations than the predicted anesthetic concentration. Thus, 5-HT2A receptors are inhibited by alcohols and volatile anesthetics, and these actions are dependent on protein kinase C.

Anesthetics↗

Comparative disinfection of secondary-treated sewage with chlorine dioxide and bromine chloride.

A comparison was made of the inactivation rates of Arcobacter butzleri, coliphages, total coliforms, fecal coliforms, fecal streptococci and heterotrophic plate count in secondary sewage effluent using chlorine dioxide (2 and 4 ppm) and bromine chloride (4 or 8 and 12 ppm) as disinfecting agents. Using these doses the ClO2 gave higher reduction percentages (on average more than 99% at 4 ppm) than those obtained with BrCl. The average values of the fecal indicators are well within the legal limits. Arcobacter butzleri was more sensitive to the disinfectants than other bacteria while fecal streptococci were seen to be more resistant. From the chemical point of view no differences were seen between the two disinfectants except that the action of ClO2 was stronger regarding BOD5 than that of BrCl. With the exception of dichloromethane, the concentration of volatile halogenated compounds showed little variation and values were often lower than detection limits.

Bromides↗

CFCS and the ozone layer.

Ozone is an important constituent of the atmosphere. Ozone forms a distinct layer in the lower stratosphere known as the ozone layer. The ozone layer acts as a fragile shield because it protects man and other life forms from exposure to harmful short-wavelength ultraviolet (UV) radiation. The agents, particularly chemical, which affect the amount of ozone present in the atmosphere have been a source of concern for more than 20 years. This has been reinforced by the dramatic decline of stratospheric ozone levels first measured in Antarctica and now apparent worldwide. The combination of routine measurements of ozone depletion, careful laboratory studies and mathematical modelling of ozone in the atmosphere, has demonstrated that the reactive fragments produced when chlorofluorocarbons (CFCs), halons and other halogenated compounds break down in the stratosphere are responsible for the ozone loss. As CFCs have widespread and sometimes apparently essential uses in modern society, there has been an intense effort to develop safe, effective replacements which have a negligible or much smaller impact on the environment. The Montreal Protocol, signed by over 140 nations, has been implemented to control and phase out the chemical compounds responsible for ozone loss.

Air Pollutants↗

[Effect of general anesthesia on complement. Effect of the atmosphere in the operating room on the immune response of anesthesiologists].

Variations in the C3 and C4 fractions of complement were studied in 15 patients who underwent surgery with either spinal anesthesia (5 cases) or general anesthesia using nitruos oxyde and a halogen compound (10 cases). Little peroperative variation was observed. An increase in C4 was observed in all cases postoperatively. Only a slight increase in C3 was observed after spinal anesthesia. The immune response of anesthetists exposed to halothane was investigated using PHA-induced lymphocyte stimulation (normal in males, elevated in females) and lymphocyte transformation to halothane and its metabolites (no evidence of allergy was observed).

Air Pollutants↗

Hepatic microsomal enzyme induction by trifluoromethyl compounds and some halogenated and nonhalogenated analogs.

Trifluoromethyl derivatives of toluene, phenothiazine, benzimidazole and DDT were administered ip to male rats for 5 days and induction of hepatic microsomal enzymes catalyzing the metabolism of EPN, p-nitroanisole and aminopyrine measured. The addition of a trifluoromethyl substituent to toluene, phenothiazine and benzimidazole increased the inducing capacity of the parent molecule on p-nitroanisole metabolism. Dihalogenation of benzene with trifluoromethyl groups, regardless of position, resulted in induction of p-nitroanisole metabolism whereas halogenation of benzene with trichloromethyl groups did not. For these compounds, the size and electron-inducing capacity of the halogenated substituent may be relative to microsomal enzyme induction.

Aminopyrine N-Demethylase↗

Historical trends in occurrence and atmospheric inputs of halogenated volatile organic compounds in untreated ground water used as a source of drinking water.

Analyses of samples of untreated ground water from 413 community-, non-community- (such as restaurants), and domestic-supply wells throughout the US were used to determine the frequency of detection of halogenated volatile organic compounds (VOCs) in drinking-water sources. The VOC data were compiled from archived chromatograms of samples analyzed originally for chlorofluorocarbons (CFCs) by purge-and-trap gas chromatography with an electron-capture detector (GC-ECD). Concentrations of the VOCs could not be ascertained because standards were not routinely analyzed for VOCs other than trichloromonofluoromethane (CFC-11), dichlorodifluoromethane (CFC-12) and 1,1,2-trichloro-1,2,2-trifluoroethane (CFC-113). Nevertheless, the peak areas associated with the elution times of other VOCs on the chromatograms can be classified qualitatively to assess concentrations at a detection limit on the order of parts per quadrillion. Three or more VOCs were detected in 100% (percent) of the chromatograms, and 77.2% of the samples contained 10 or more VOCs. The maximum number of VOCs detected in any sample was 24. Modeled ground-water residence times, determined from concentrations of CFC-12, were used to assess historical trends in the cumulative occurrence of all VOCs detected in this analysis, as well as the occurrence of individual VOCs, such as CFC-11, carbon tetrachloride (CCl(4)), chloroform and tetrachloroethene (PCE). The detection frequency for all of the VOCs detected has remained relatively constant from approximately 1940 to 2000; however, the magnitude of the peak areas on the chromatograms for the VOCs in the water samples has increased from 1940 to 2000. For CFC-11, CCl(4), chloroform and PCE, small peaks decrease from 1940 to 2000, and large peaks increase from 1940 to 2000. The increase in peak areas on the chromatograms from analyses of more recently recharged water is consistent with reported increases in atmospheric concentrations of the VOCs. Approximately 44% and 6.7% of the CCl(4) and PCE detections, respectively, in pre-1940 water, and 68% and 62% of the CCl(4) and PCE detections, respectively, in water recharged in 2000 exceed solubility equilibrium with average atmospheric concentrations. These exceedences can be attributed to local atmospheric enrichment or direct contaminant input to ground-water flow systems. The detection of VOCs at concentrations indicative of atmospheric sources in 100% of the samples indicates that untreated drinking water from ground-water sources in the US recharged within the past 60 years has been affected by anthropogenic activity. Additional inputs from a variety of sources such as spills, underground injections and leaking landfills or storage tanks increasingly are providing additional sources of contamination to ground water used as drinking-water sources.

Atmosphere↗

Nephrotoxicity of halogenated vinyl cysteine compounds.

S-(1,2-dichlorovinyl) cysteine (DCVC), is a potent nephrotoxin. In order to determine if other vinyl cysteine conjugates were nephrotoxic, halogenated vinyl cysteines, HVC-1 and HVC-2, were prepared from chlorotrifluoroethylene (CTFE), a fluorocarbon monomer, or chlorotifluoroethylene, a metabolite of halothane, respectively. Three days after receiving DCVC (5-10 mg/kg), CD-1 mice developed focal renal tubular necrosis. Mice treated with HVC-1 or HVC-2 (5-10 mg/kg) also developed renal necrosis by 3 days post exposure. HVC-1 was not as potent as DCVC with the necrosis limited to the pars recta. At equivalent doses HVC-2 caused less necrosis of the pars recta than HVC-1. The degree of nephrotoxicity by all three compounds exhibited a dose-response from 1-25 mg/kg. Doses greater than 25 mg/kg were often lethal within 3 days and the mice had a complete zonal necrosis of the renal cortex and a two-fold increase in kidney weight. Structural analogues, S-(chlorethyl) or S-(hydroxyethyl) cysteine, did not cause renal necrosis in mice at doses up to 200 mg/kg. These studies indicate that the enzymes reportedly responsible for converting DCVC to a nephrotoxic intermediate will also bioactivate other halogenated vinyl cysteines.

Animals↗

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↗