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PubMed1975

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↗

PubMedDate not supplied

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↗

PubMed1978

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↗

PubMed1979

Comparison of the acute toxicity of clioquinol, histamine, and chloroform in different strains of mice.

The oral LD50'S of clioquinol, histamine and chloroform and the intravenous LD50 of histamine were determined separately in male and female mice of the Tif : MAGf (SPF), Tif : MF2f (SPF), C3H/Tif Bomf, DBA2/J Bomf, C57Bl/6J/Bomf and A/J Bomf strains. Mice of the Tif : MAGf (SPF) outbred strain and the Tif : MF2f(SPF) hybrids tended to be more resistant than the inbred strains, with exception of C57Bl/6J/Bomf, which proved least susceptible to the lethal effects of the tested preparations. The toxicity of chloroform was more pronounced in the males than in the females, and C3H/Tif Bomf proved more susceptible than all other strains. The toxicity of clioquinol and histamine was not related to sex.

Animals↗

PubMed1977

Evidence supporting the identity of beef heart mitochondrial chloroform-released adenosine triphosphatase (ATPase) with coupling factor I.

Highly purified mitochondrial chloroform-released beef heart ATPase had molecular weight 330 000, five bands (alpha, beta, gamma, delta, epsilon) in sodium dodecyl sulfate gel electrophoresis and could restore the oxidative-phosphorylation function of A particles. Maximal inhibition (90%) of the enzyme by N,N'-dicyclohexylcarbodiimide was achieved at a molar ratio of inhibitor to protein of 30 : 1. Chloroform introduced into an aqueous solution of beef heart coupling factor I protected it from cold inactivation.

Adenosine Triphosphatases↗

PubMed1979

Ability of calf brain synaptic membranes to bind [35S]taurine to their triton X-100 and chloroform extracts.

A protein fraction containing reducing sugars was prepared from calf brain synaptic membranes with 0.5% Triton X-100, and another fraction containing bound phosphorus with a 2 : 1 chloroform--methanol mixture. Both protein fractions bound small amounts of [35S]taurine, the first fraction about 25 pmol/g protein and the second about 220 pmol/g protein. The Triton X-100 extract represented 13.8% of the membrane proteins, but the chloroform--methanol extract only 0.9%. The binding of taurine to the Trition X-100 extract was temperature sensitive, but was only slightly inhibited by hypotaurine and beta-alanine.

Alanine↗

PubMed1978

A method of gas chromatography using electron-capture detection for the determination of blood concentrations of halothane, chloroform and trichloroethylene.

A method of gas chromatography using electron-capture detection for the determination of the concentration of the halogenated anaesthetic agents halothane, chloroform and trichloroethylene in blood is described. The accuracy of the analysis (measured blood concentration as a percentage of the calculated concentration) was: Halothane (11 blood samples in the range 37.9-6.00 mg/100 ml), mean 100.7 (SD 2.27), range 97.3-104.0; (12 samples in the range 0.164-0.0045 mg/100 ml), mean 98.8 (SD 6.80), range 90.7-111.1. Chloroform (five blood samples in the range 63.6-7.40 mg/100 ml), mean 100.4 (SD 1.30), range 99.3-102.5. Trichloroethylene (five blood samples in the range 20.6-13.2 mg/100 ml), mean 101.6 (SD 1.60), range 99.6-104.0.

Chloroform↗

PubMedDate not supplied

Association between chloroform levels in finished drinking water supplies and various site-specific cancer mortality rates.

This paper discusses some of the statistical and biological problems that are likely to be encountered when an indirect or ecological approach is used to assess the possible public health impact of general population exposures to environmental agents. For purposes of illustration, the potential association between various site-specific cancer mortality rates and chloroform levels in public drinking water supplies was considered. The analyses that were performed demonstrated that, for the data sets under consideration, there were some definite associations between chloroform levels and cancer mortality for specific sites such as the rectum-intestine and bladder. However, the marked extent to which these results were dependent on (1) the weighting scheme adopted in the analysis, (2) the presumed appropriateness of the data, and (3) the characteristics of the statistical model was also clearly illustrated. Because of these dependencies the quantitative, causal interpretation of results generated from an indirect study would appear to be a very tenuous and questionable practice in most instances.

Chloroform↗

PubMed1979

Whole-body autoradiography and allied tracer techniques in distribution and elimination studies of some organic solvents: benzene, toluene, xylene, styrene, methylene chloride, chloroform, carbon tetrachloride and trichloroethylene.

Whole-body autoradiography has been used to study the distribution and fate of 14C-labeled benzene, toluene, xylene, styrene, methylene chloride, chloroform, carbon tetrachloride and trichloroethylene in mice after inhalational exposure. Total radioactivity, including the volatile part of the solvents were registered by autoradiography of dried, evaporated tape-fastened sections. In addition, dried, evaporated tape-fastened sections were extracted with water, trichloroacetic acid and a series of organic solvents and autoradiographed to register organs where metabolites were firmly bound. In another facet of the study, the quantitative elimination of the solvents and their metabolites via various routes was investigated. The expiration of unchanged solvents was subject to mathematical and computerized compartmental pharmacokinetic analysis. All solvents were rapidly taken up in fatty and nervous tissues where they were retained for different periods of time largely dependent on their fat solubility. Unexpectedly long retention times were noted for the chlorinated solvents, particularly for chloroforn, which showed a specific long-term retention in the cerebellum, meninges and spinal nerves, indicating interactions with specific nervous tissue receptors. Solvent metabolites appeared rapidly in several organs, mainly the liver and kidney, and were excreted both via urine and bile. Toluene and xylene metabolites were completely extractable whereas firmly bound metabolites were registered after inhalation of benzene, styrene and all chlorinated solvents, notably in the liver and kidney but also in the bronchi of the lung. Three-compartment pharmacokinetics were observed for the majority of the solvents selected for study although a two-compartment model was found to fit the elimination rate curves for styrene, methylene chloride and chloroform in the exhaled air. The fat solubility of the solvents was found to influence their pharmacokinetics since lower rate constants were generally obtained for the expiration of more fat soluble solvents.

Adipose Tissue↗

PubMedDate not supplied

Intrachain reactions of a pair of reactive groups attached to polymer ends. 3. Intrachain charge-transfer complex on polysarcosine chains having terminal electron donor and terminal electron acceptor groups in chloroform solution.

Polysarcosine having a terminal p-dimethylaminoanilide group and a terminal 3,5-dinitrobenzoyl group was synthesized. The number-average degree of polymerization n was varied from 6 to 25. In chloroform solution this polymer showed a distinct absorption band around 455 nm, which was attributed mostly to intramolecular charge-transfer interactions. The extinction coefficient of the charge-transfer complex was determined for low molecular weight model compounds. Using the same extinction coefficient, the fraction of polymers forming intrachain charge-transfer complex was evaluated at infinite dilution. The fraction was about 0.15 for n = 6 and decreased asymptotically with increasing n finally to 0.03 for n = 25. These values are almost 20-100 times as large as those estimated from the Monte Carlo calculation and on the basis of the intramolecularly catalyzed hydrolysis of polysarcosine chain. This indicates that the cyclized conformations of polysarcosine chain are greatly stabilized by the formation of intrachain charge-transfer complex. The fraction of the cyclized polymer was decreased with increasing temperature for short chains. The thermodynamic parameters characterizing the conformational change required for cyclization in chloroform were obtained and compared with those for the same reaction in ethanol solution, as well as those for the intramolecularly catalyzed hydrolysis on polysarcosine chain in aqueous solution.

Chemical Phenomena↗

PubMed1977

Purification and properties of adenosine triphosphatase solubilized from beef heart mitochondria by chloroform.

Soluble, oligomycin-insensitive ATPase released from beef heart mitchondria by chloroform extraction can be further purified by Sepharose 6B gel filtration. This purification increases enzyme activity 4--5 times (100-130U/mg). According to specific activity, high purity and ability to reconstitute oligomycin-sensitive complex, isolated ATPase is quite comparable with enzyme preparations isolated by other methods.

Adenosine Triphosphatases↗

PubMed2026

Stable chloroform emissions in southeastern China: insights from recent observations.

Chloroform (CHCl3) is a short-lived ozone-depleting substance not currently regulated under the Montreal Protocol. Due to the unique meteorological conditions in East Asia, CHCl3 emitted in this region has a greater potential to reach the stratosphere and contribute to ozone depletion. As an essential component of national CHCl3 emissions, southeastern China has attracted increasing attention. However, long-term observational data in this region remain relatively scarce, with no updates since 2020. In this study, we continuously measured atmospheric CHCl3 concentrations at a remote monitoring station in southeastern China from 1 June 2023 to 31 May 2025. Frequent concentration enhancements were observed during the monitoring period, with mixing ratios ranging from 9.3 to 134.1 ppt and an average value of 36.8 ± 19.7 ppt. Back-trajectory analysis indicated that air masses associated with elevated CHCl3 levels primarily originated from coastal industrial provinces in eastern China. Using the Potential Source Contribution Function and Concentration Weighted Trajectory methods, we identified the Yangtze River Delta (Jiangsu, Anhui, and Zhejiang Provinces) and Jiangxi Province as dominant source regions. Emissions of CHCl3 in southeastern China were estimated using the Tracer Ratio Method to be approximately 30.1 ± 5.3 Gg/yr from 2023-06-01 to 2025-05-31, indicating overall stability relative to earlier estimates and no apparent upward trend. These findings provide updated insights into the current status of CHCl3 emissions in southeastern China and highlight the need for continued monitoring and emission assessment of CHCl3 in East Asia, given its unregulated status and implications for ozone layer recovery.

Air Pollutants↗

PubMed1976

The effect of chloroform on Brucella abortus agglutinins in whey.

Defatting milk for the Brucella abortus whey agglutination test with chloroform caused some reduction in the titre in i.u./ml. in 42 of 57 samples and this reduction exceeded 50% in seven. Though this procedure will probably rarely affect the final interpretation of the test defatting the milk by centrifugation is preferred.

Agglutination Tests↗

PubMed1978

Selective modification of the renal and the hepatic toxicities of chloroform by induction of drug-metabolizing enzyme systems in kidney and liver.

Renal and hepatic microsomal enzyme activities were measured in ICR male mice treated with phenobarbital (PB), 3-methylcholanthrene (3MC), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or polychlorinated biphenyls (PCB). The effect of these agents on subsequently administered single doses of chloroform (CHCI3) were also determined. 3MC, TCDD and PCB increased renal as well as hepatic microsomal enzyme activities. PB increased hepatic but not renal microsomal enzyme activities. The hepatotoxicity of CHCI3 was increased by pretreatment with PB but decreased by pretreatment with TCDD. 3MC and PCB were without effect on CHCI3-induced liver damage. Pretreatment with 3MC, TCDD or PCB reduced the renal toxicity of CHCI3, but PB had no effect on CHCI3-induced kidney damage. Since at least one product of enzymatic metabolism of CHCI3 is believed to be a toxic, reactive intermediate the differential effects of inducers of microsomal drug-metabolizing enzyme activities on the renal and hepatic toxicities of CHCI3 strongly suggest that the CHCI3 metabolite(s) ultimately responsible for renal and hepatic damage are not generated at a common site. That is the metabolite responsible for hepatic is probably generated in the liver and the metabolite responsible for renal damage is probably generated in the kidney.

Animals↗

PubMed1976

Mechanisms involved in enhancement of plasma fibrinolytic activity by chloroform.

The effects of a single 1-min extraction with chloroform (CHCl3) on plasma fibrinolytic activity has been examined by 125I-fibrin solid phase assay, using normal plasma and plasma depleted of plasminogen (PLG) by lysine-Sepharose affinity chromatography. Fibrinolytic activity of normal plasma is increased (40%-175%), and more than 95% of antiplasmin activity is removed. The increase is demonstrable in PLG-depleted plasma, and is not inhibited by tranexamic acid (0.01 M). Purified PLG is not activated to plasmin by ChCl3 treatment. Bio-Gel A 0.5 m fractionation of CHCl3-extracted, PLG-depleted plasma reveals fractions with the following activities: (1) streptokinase-activatable, PLG-independent fibrinolytic activities; (2) PLG activator activities; and (3) plasmin-stimulated but PLG-independent fibrinolytic activities, which include activities inhibited by hexadimethrine bromide and which cofractionate in part with plasmin-stimulated procoagulant activities. In addition, similar fractionation of nonextracted plasma reveals two non-plasmin fibrinolytic activities (approximately 30,000 and 13,000 daltons) activated by streptokinase and plasmin, respectively. The findings indicate that the enhanced fibrinolytic activity resulting from CHCl3 treatment is independent of plasmin as the ultimate fibrinolytic enzyme, although activities stimulated by plasmin may contribute, and that such treatment is a useful maneuver for study of PLG-dependent and PLG-independent fibrinolytic mechanisms, and their interactions.

Blood Coagulation↗

PubMed1978

[Comparison of the cytotoxicity of chloroform on mouse L cells by measurement of proteins and chromium 51 release].

The authors describe a new cytotoxicity test based on the classical measurement of the residual proteins after a contact time of 4 days between the produit tested and the mouse L cells. The results are expressed as a cytotoxic dose 50 with a confidence limit for the 95% threshold after a statistical treatment of the analytical data by a computerized method. For chloroform, this method is more sensitive that the classical cytotoxicity test involving the chrom 51 release.

Chloroform↗

PubMed1977

Reduction of nitro-BT by some components of the chloroform-methanol extract of the grey matter of the rat brain.

An attempt was made to extract the substance present in the nerve fibres of the cerebral cortex and basal ganglia which reduced Nitro-BT in alkaline medium pH 9-5 [4,5]. The investigations were performed on 40 white Wistar rats of both sexes and ca. 200 g of body weight. The brains taken for studies were fixed in Baker's formalin for 1,5 hr, thereafter grinded and homogenized in chloroform-methanol solution supplemented up to 100 ml of final volume after homogenisation. Thus prepared solution was left for 24 hr at 4 degrees C temperature and than centrifuged 2000 g/min. The extract was evaporated and the sediment further investigated. The following fraction were received: 1. fraction soluble in aceton, 2. fraction soluble in ethylalcohol, 3. fraction soluble in ether, 4. fraction soluble in water and 5. the sediment. Each fraction was incubated with a standard medium containing Nitro-BT. After incubation the amount of reduced Nitro-BT in each of the incubation medium was spectrophotometrically measured. The most intense reduction was found in the incubation medium with the water fraction. The spectrophotometrically determined reduction of Nitro-BT of the water fraction compared with that of the gangliosides solution were similar. The addition into the incubation media biogenic amines and N,N-diethyl-p-phenylenediamine enhances the reduction of Nitro-BT significantly. According to the results obtained an interference of gangliosides and of the investigated amines in the reduction of Nitro-BT is suggested.

Animals↗

PubMed1975

[Determination of bilirubin in the amniotic fluid by means of the chloroform-extraction method].

A reproducible method for the determination of bilirubin in amniotic fluid by measuring the extinction of the the chloroform extract is described. The measurements can be carried out by means of a simple spectrophotometer. In case of extraction of amniotic fluid containing blood informative results are obtained as well. Since the extinction values are equal to the deltaE-values it is possible to determine the degree of morbus haemolyticus fetalis using the schema of Liley.

Amniotic Fluid↗