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Photooxidation of papaverine, papaverinol and papaveraldine in their chloroform solutions.

Papaverine hydrochloride, papaverinol, and papaveraldine chloroform solutions were exposed to UV light of 254 nm in atmospheric, aerobic and anaerobic (helium) conditions. The same degradation products appear (TLC) in the above papaverine hydrochloride chloroform solutions. However, the rate of papaverine hydrochloride degradation processes is enhanced as a function of oxygen pressure. Papaverinol and papaveraldine photooxidation products are essentially not different from those observed in the above papaverine hydrochloride solutions. However, the amount of an unknown brown degradation product (X) is the greatest in the papaverinol chloroform solution degraded. That brown compound was previously observed in papaverine either hydrochloride or sulfate injection solutions on their storage even when protected from daylight. The preliminary X product structure development was undertaken (TLC, molecular weight, elemental analysis, UV/VIS, IR and 13C MAS NMR spectroscopy).

Chloroform↗

[Influence of the mixed disinfectant of ClO2 and Cl2 on formation of chloroform].

The study on influence of mixed solution of ClO2 and Cl2 on formation of chloroform from 9 THMs precursors, such as fulvic acid (FA), resorcinol, phloroglucinol and cresorcinol etc. under conditions of different ClO2/Cl2 ratio, content of precursors, reaction pH, reaction time and reaction temperature etc. was studied. Results showed that as the mass percentage of ClO2 in the mixed disinfectant was increased, the amount of chloroform formed was reduced; such as when mass percentages of ClO2 were 25%, 50% and 75%, CHCl3 formed reduced 55%-65%, 70%-86% and 80%-93% respectively; until ClO2 was 90%, reduction of CHCl3 reached 95%-99%. In order to control the formation of chloroform thoroughly, mass percentage of ClO2 must be higher than 90%. This provided important scientific base for the necessity of using highly pure ClO2 in disinfection and developing generator which produced high quality ClO2.

Chlorine↗

[The introduction of chloroform anesthesia in Madrid. Notes for studying its history].

Until present, the introduction of chloroform anesthesia in Madrid has not been specifically studied by any author. Therefore, knowledge of the events related to this happening is lacking. We have studied this chapter of our history by analyzing primary documents and articles published at the daily press, political press, and scientific journals of Madrid during 1847 to 1848. This investigation allowed us to follow the most relevant news dealing with the discovery of the drug and with its first experimental and clinical applications in Madrid. Based on the present bibliographic material we could establish a chronologic report of all surgical interventions using chloroform that were performed in Madrid. We conclude that albeit surgeons in Madrid were not the first to use chloroform in Spain, they were, however, the ones who most extensively used it. Their contribution was of relevance in the settlement of the new anesthetic agent in Spain.

Anesthesia, General↗

[Hygienic evaluation of the combined effect of portable water chloroform].

The paper considers the significance of complex entrance of chloroform from portable water into the human body (enterally, inhalationally, and through the intact skin). It shows it necessary to toughen the maximum permissible concentration (MPC) of chloroform in the portable drinking, by taking into account of the multiplicity of routes of its action on the population. The authors present the results of their own investigations of the levels of chloroform in the air of bath and shower rooms before and after taking a shower and filling the bath with water, as well as in the airspace layer above the water of an indoor swimming pool, by using chromatographic mass-spectrometry.

Carcinogens↗

Estimation and control of atmospheric emissions of chloroform and dichloromethane due to laboratory activity.

In Japanese universities, the management of chemical reagents has become an important issue in preserving the environment and the health of students and researchers. It is thus necessary to estimate the levels of chemical emissions into the environment and to measure working-environment chemical levels in laboratories. However, there are many laboratories in universities using many chemical reagents for their own needs. Hence, it is difficult for universities to quantitate the amount of chemicals on campus, and there is a lack of information about laboratory environment chemical levels. In this study, the material balance of chloroform and dichloromethane (DCM) in Kyoto University was examined, and the emission rates of chloroform and DCM were estimated to be 37-50% and 50-70%, respectively. These chemicals were thought to be volatilized mainly through reduced-pressure distillation. However, it was found that there was a loss of chemicals due to volatility, which researchers were unaware of, such as that during solvent recovery under reduced pressure and volatilization from containers of organic waste liquid. On the other hand, working-environment chemical levels were measured in several laboratories which used chloroform and DCM frequently. Even in such laboratories, the average concentrations of these chemicals were approximately 1 ppm at most measurement points.

Air Pollution↗

The role of microsomal hydroxylases in the modification of chloroform hepatotoxicity in rats.

Male rats have a greater microsomal amidopyrine N-demethylase activity per unit weight of liver, a shorter hexobarbitone sleeping time and are more susceptible to the hepatotoxic effect of chloroform than female rats. Phenobarbitone sodium, phenylbutazone and DDT induce microsomal amidopyrine N-demethylase in the liver of the male rat and reduce hexobarbitone sleeping time. Chlorpromazine is less effective in this respect. Phenobarbitone, phenylbutazone and, to a lesser extent, chlorpromazine potentiate the hepatotoxic effect of chloroform in male rats. SKF 525A, sodium diethyl-dithiocarbamate and carbon disulphide increase hexabarbitone sleeping time in male rats and protect to varying degrees against the hepatotoxic effect of chloroform.

Animals↗

Efficient and effective root canal retreatment without chloroform.

A root canal retreatment technique is described which eliminates the need for chloroform as a gutta percha solvent. This technique utilizes the gutta percha softening actions of both a self-heating instrument and the heat-potentiated solvent action of eucalyptol. In addition, sonics/ultrasonics and/or Gates-Glidden drills are suggested as useful adjuncts to canal debridement during re-preparation of the canal system. Given the controversy regarding the toxicity of chloroform, both for dental patients and dental personnel, practitioners may wish to consider using this retreatment technique to eliminate chloroform from endodontic retreatment procedures, while still achieving effective, efficient root canal retreatment.

Chloroform↗

Stroma-free hemoglobin solutions purified by chloroform and pasteurization.

Several approaches to the processing of native stroma-free hemoglobin solutions (SFH) were reconsidered regarding present requirements for SFH production and quality. Treatment of outdated red blood cells (RBCs) with chloroform and/or by pasteurization were evaluated for technical ease, speed and efficacy in removing stromata, phospholipids and non-heme proteins from RBC hemolysates. The influence of both procedures upon spontaneous hemiglobin formation in stored, preferably freeze-dried SFH was compared. Among other analytical methods, sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS PAGE) and isoelectrofocusing were used for mutual comparison of the purification procedures. Pasteurized samples were significantly better purified, more homogeneous but also more susceptible to spontaneous oxidation, probably due to heat inactivation of enzymic scavengers of oxygen radicals. On the other hand, the chloroform-treated, unheated SFH samples were less purified from non-heme proteins, but were more stable. Fructose and sucrose were equally active in protecting SFH from oxidation during freeze-drying. At present, the easy chloroform treatment and freeze-drying of thus purified SFH with fructose of sucrose seems to offer a plausible technological compromise which merits further investigation.

Chloroform↗

Histopathology of chloroform-induced inner ear damage.

Inner ear function loss was caused in guinea pigs and rats by injecting chloroform into the middle ear. After symptoms for cochlear and vestibular deficit had been registered, the animals were permitted to survive for one day to five months. Ear histopathology was then studied in celloidin sections. In both species, hair cells and afferent nerve fibers were intact at all survival times. The acute stage of functional loss in guinea pigs was associated with inner ears of normal histological appearance. Within days after chloroform injection a severe otitis media developed which led to fibrous occlusion of the round window and eventually to new bone growth in the middle ear space around the otic capsule. A secondary labyrinthitis was also observed, resulting in endolymphatic hydrops at longer survival times. Different histopathological changes were seen in rats. The tectorial membrane appeared swollen in all cases, the swelling being more severe in more apical turns at longer survival times. It is concluded that only secondary sequela of the initial functional insult can be detected by standard light microscopic histopathology. Chloroform does not cause a chemical labyrinthectomy as previously assumed, although it is severely ototoxic.

Animals↗

Comparison of ether and chloroform for Soxhlet extraction of freeze-dried animal tissues.

Chloroform was a satisfactory replacement for ether in solvent extraction for lipid determination in freeze-dried animal tissues, although values obtained were not identical. Fat content of tissues used in this study ranged from less than 10 to more than 95%. Chloroform has the great advantage of being fireproof, but proper fume hoods should be used. An antifoaming agent should be added to chloroform, both in the Soxhlet apparatus and when it is redistilled.

Adipose Tissue↗

Safety evaluation of toothpaste containing chloroform. II. Long term studies in rats.

The results of a preliminary rangefinding 13-wk oral toxicity study and of two longer term studies on chloroform in toothpaste base are reported. Significant changes in serum enzymes and certain haemotological parameters were seen at the higher dose-levels in the rangefinding study. Intercurrent disease made it necessary to terminate the first long-term experiment prematurely after 1 yr. No evidence of serious toxicity was recorded. In the second long-term experiment, groups of 50 caesarian-derived SPF Sprague-Dawley rats of each sex received either the equivalent of 60 mg CHCl3/kg/d in toothpaste base or the vehicle only, by gavage on 6 d/wk for 80 wk and were then observed for up to a further 15 wk. Chloroform-treated rats of both sexes survived better than the controls, though both groups had a high incidence of non-neoplastic respiratory and renal disease. Female rats gave a consistent finding of decrease in plasma cholinesterase, shown to be related to activity against butyrylcholine but not acetyl-beta-methylcholine. Tumours of various sites were seen in 39 percent of chloroform-treated rats of both sexes examined histologically, compared with 38 percent of vehicle controls. There were no treatment-related effects on the incidence of liver or kidney tumours. Histologically-malignant mammary tumours were reported in more treated than control rats, but the difference in incidence was not statistically significant.

Animals↗

Chloroform inactivation of reovirus hemagglutinins.

The hemagglutinin of all three types of reovirus was inactivated by chloroform with little or no diminution in virus infectivity. Albumin and other proteins protected the hemagglutinin from inactivation by chloroform. When crude reovirus suspensions were centrifuged in a sucrose density gradient, two hemagglutinin fractions were collected. The fraction which sedimented more rapidly contained the bulk of infectious virus, but both lost hemagglutinin activity when extracted with chloroform. Ether extraction of the fractions did not reduce either the infectivity or hemagglutinin titre.

Animals↗

Chloroform-induced fibrinolysis. Its dependence on Hageman factor, plasma prekallikrein, and high molecular weight kininogen.

Incubation of normal human plasma or its euglobulin fraction with chloroform enhances the generation of proteolytic activity attributable to plasmin. The mechanisms involved remain unclear. Earlier, plasmin formation was found to be impaired in the chloroform-treated euglobulin fraction of Hageman trait plasma. We now demonstrate sharply reduced generation of fibrinolytic and caseinolytic activities in prekallikrein-deficient (Fletcher trait) and HMW kininogen-deficient (Fitzgerald trait) plasmas as well. These defects were corrected by addition of the missing factors. In addition, precipitation of the euglobulin fraction of plasma activated small but measurable amounts of HF. With the use of 125I-HF, cleavage of the native molecule into its amino-terminal and carboxy-terminal fragments occurred pari passu with the generation of plasmin. These experiments suggest that one pathway through which HF can bring about formation of plasmin in chloroform-treated euglobulin fractions involves the participation of plasma prekallikrein and HMW kininogen, presumably through mechanisms similar to those evoked by surface activation of HF.

Animals↗

[Antiphagocytic activity of sera treated with organic solvents (chloroform, ether)].

The opsonization of C. albicans by means of sera treated with chloroform and ethyl ether resulted in significantly decreased values of PMN leucocyte phagocytic activity. In contrast to ethyl ether treated sera (decrease of phagocytic activity about 45%), chloroform processed sera possessed increased antiphagocytic activity (decrease of phagocytic activity about 63%). Significant changes were observed in the candidacidal capacity to C. albicans (decrease about 50%) and in the capacity of NBT (INT) reduction measured spectrophotometrically (decrease about 66% in chloroform treated sera and about 42% in ethyl ether treated sera). (Fig. 1, Ref. 22.)

Candida albicans↗

Studies on the toxicity and maximum allowable concentration of chloroform.

Chloroform has obvious hepato-, nephro-toxicity and carcinogenicity. In order to get necessary data for recommendation of maximum allowable concentration of chloroform in workplace, a series of studies were carried out. The results showed that exposed workers mainly distributed in the industries of perspex processing, production of refrigerants, drugs and pesticides. The exposure level ranged 4.27-147.91 mg/m3 in 119 air samples collected from 3 representative worksites, with 45.4% air samples below 20 mg/m3. The workers exposed to chloroform at 29.51 mg/m3 had slight liver damage indicated by the higher rates of abnormal serum prealbumin and transferrin levels than those of control workers. The neurobehavioral functions of these workers were also obviously affected, manifested as increases in scores of passive mood states and dose-related negative changes in neurobehavioral testing. The observed effect threshold concentration of subacute inhalation in rats was 592 mg/m3 according to the observation on the biochemical changes in liver tissue and abnormal activities of serum enzymes. Mainly based on the above results, we recommended 20 mg/m3 as the Maximum Allowable Concentration in workplace in China at present.

Adult↗

Chiral purity test of metoprolol enantiomer after derivatization with (-)-menthyl chloroformate by reversed-phase high performance liquid chromatography.

A reversed-phase high-performance liquid chromatographic method was developed to determine the optical purity of metoprolol enantiomers. The enantiomers were converted to diastereomeric derivatives using (-)-menthyl chloroformate reagent. Separation of the enantiomers as diastereomers was achieved by reversed-phase HPLC within 30 min using Inertsil C8 column. This method allowed determination of 0.05% of either enantiomer in the presence of its stereoisomer and method validation showed adequate linearity over the required range. Owing to the reaction condition during the derivatization with (-)-menthyl chloroformate, the possibility of racemization had to be established. Different ratios of (S)-(-)-metoprolol and (R)-(+)-metoprolol were prepared. Enantiomeric separation of these mixtures took place on a chiralcel OD column or, after derivatization with (-)-menthyl chloroformate, on a C8 column. The results from the these two independent separation systems were compared with trace racemization and were in very good agreement. No racemization was found during the experiment.

Chromatography, High Pressure Liquid↗

Affinity chromatography of H+-translocating adenosine triphosphatase isolated by chloroform extraction of Rhodospirillum rubrum chromatophores. Modification of binding affinity by divalent cations and activating anions.

1. ATPase isolated from Rhodospirillum rubrum by chloroform extraction and purified by gel filtration or affinity chromatography shows three bands (alpha, beta and gamma) upon electrophoresis in sodium dodecyl sulphate. 2. Ca2+-ATPase activity of the preparation is inhibited by aurovertin and efrapeptin but not by oligomycin. Activity may be inhibited by treatment with 4-chloro-7-nitrobenzofurazan and subsequently restored by dithiothreitol. 3. The enzyme fails to reconstitute photophosphorylation in chromatophores depleted of ATPase by sonic irradiation. 4. Most of the active protein from the crude chloroform extract binds to an affinity chromatography column bearing an immobilised ADP analogue but not to a column bearing immobilised pyrophosphate. 5. In the absence of divalent cations, a component with a very high specific activity for Ca2+-ATPase is eluted from the column by 1.6 mM ATP. This protein migrates asa single band on 5% polyacrylamide gel electrophoresis and only possesses three subunits. At 12 mM ATP an inactive protein is eluted which does not run on acid or alkali polyacrylamide gels and shows a complex subunit structure. 6. ATPase preparations prepared by acetone extraction or by sonic irradiation of chromatophores may also be purified 10-fold by affinity chromatography. 7. The inclusion of 5 mM MgCl2 or CaCl2 during affinity chromatography of chloroform ATPase increases the capacity of the column for the enzyme and demands a higher eluting concentration of ATP. 8. When the enzyme is more than 90% inhibited by efrapeptin or 4-chloro-7-nitrobenzofurazan, the binding characteristics of the enzyme are not affected. 9. 10 mM Na2SO3, which greatly stimulates the Ca2+- and Mg2+-dependent ATPase activity of the enzyme and increases Ki (ADP) for Ca2+-ATPase from 50 to 850 micron, prevents binding to the affinity column. Binding may be restored by the addition of divalent cations. 10. Na2SO3 increases the rate of ATP hydrolysis, ATP-driven H+ translocation and ATP-driven transhydrogenase in chromatophores. 11. It is proposed that anions such as sulphite convert the chromatophore ATPase into a form which is a more efficient energy transducer.

Adenosine Triphosphatases↗

Limited extent of stereochemical conversion of chiral non-steroidal anti-inflammatory drugs induced by derivatization methods employing ethyl chloroformate.

A potential problem with chiral derivatization is the possibility of stereochemical conversion during the derivatization reaction. This possibility has been examined using the non-steroidal anti-inflammatory drugs ibuprofen, ketoprofen, etodolac and flurbiprofen. To avoid possible interference from stereochemical impurities, male Sprague-Dawley rats were dosed intraperitoneally with the S enantiomer (100 mg/kg) of each drug and the R enantiomer of etodolac. Blood samples were taken 4 h afterwards. The plasma samples were analyzed using published stereospecific methods involving chiral derivatization with ethyl chloroformate followed by either R-(+)-alpha-phenylethylamine or L-leucinamide. For all the drugs examined, the percentage of formation of the antipode was between 1.0 and 5.8%. In vitro studies of the R and S enantiomers demonstrate that the apparent extent of conversion is inversely related to the concentration of ethyl chloroformate present during the derivatization reaction for ibuprofen, ketoprofen and flurbiprofen but not for etodolac. However, both the R and S enantiomers appear to be inverted to the same extent in the presence of ethyl chloroformate. These results suggest that the degree of stereochemical conversion induced by these assay procedures is small and would not contribute significantly to analytical error in the absence of a large difference in concentrations of the enantiomers.

Animals↗