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PubMed1999

Extraction of chloroform and methylene chloride in human whole blood and urine by headspace solid phase microextraction (SPME).

Chloroform and methylene chloride were extracted from human whole blood and urine by headspace solid phase microextraction (SPME) using a Carboxen/polydimethylsiloxane (Carboxen/PDMS) fibre before capillary gas chromatography (GC)/flame ionization detection (FID). Whole blood or urine was placed in a vial and mixed with distilled water. The vial was heated at 30 degrees C, and the solvents were extracted from the headspace by SPME. The extraction efficiencies of chloroform and methylene chloride from whole blood were 40.3% and 35.8%, respectively; those for urine were 57.0% and 43.6%, respectively. The calibration curves for chloroform were linear in the range of 1-8 micrograms/ml for blood and urine samples, and those for methylene chloride in the range of 0.5-8 micrograms/ml. The detection limits for both compounds were 0.3 microgram/ml for whole blood and 0.2 microgram/ml for urine. The headspace SPME with Carboxen/PDMS fibre coupled with GC/FID seems useful for analyses of chloroform and methylene chloride in forensic toxicology and environmental chemistry.

Blood Chemical Analysis↗

PubMed1991

Chloroform bioactivation leading to nucleic acids binding.

Chloroform was bound covalently to DNA, RNA and proteins of rat and mouse organs in vivo after i.p. injection. Covalent Binding Index values of rat and mouse liver DNA classify chloroform as a weak initiator. Labelings of RNA and proteins from various organs of both species were higher than that of DNA. In an in vitro cell-free system, chloroform was bioactivated by cytochrome P450-dependent microsomal fractions, by cytosolic GSH-transferases from rat and mouse liver, and particularly by the latter enzymes from mouse lung. This observation suggests that GSH plays a role in the binding of chloroform metabolites to DNA. The presence of both microsomal and cytosolic enzymatic systems in the standard incubation mixture generally led to an additive or synergistic bioactivating effect for rat and mouse, respectively.

Animals↗

PubMed1997

Chloroform-induced insanity defence confounds lawyer Lincoln.

During an 1857 trial, the defence claimed that the accused should be absolved of wilful murder because an overdose of chloroform during surgery induced insanity. In a rare appearance as a prosecutor, Abraham Lincoln tried the case for the State of Illinois. Expert medical witnesses testified about the side effects of chloroform and chloroform-induced insanity. Significantly, Lincoln was not knowledgeable about medical jurisprudence and overlooked potential sources of evidence and expert witnesses. Defence lawyers presented an impressive array of physicians to testify about insanity, about chloroform and about the results of an overdosage during anaesthesia. Considering the state of scientific knowledge at the time, the trial was notable.

Chloroform↗

PubMed2006

Antidiabetic and renoprotective effects of the chloroform extract of Terminalia chebula Retz. seeds in streptozotocin-induced diabetic rats.

BACKGROUND: Terminalia chebula (Combretaceae) has been widely used in Ayurveda for the treatment of diabetes. In the present investigation, the chloroform extract of T. chebula seed powder was investigated for its antidiabetic activity in streptozotocin-induced diabetic rats using short term and long term study protocols. The efficacy of the extract was also evaluated for protection of renal functions in diabetic rats. METHODS: The blood glucose lowering activity of the chloroform extract was determined in streptozotocin-induced (75 mg/kg, i.p.; dissolved in 0.1 M acetate buffer; pH 4.5) diabetic rats, after oral administration at the doses of 100, 200 and 300 mg/kg in short term study. Blood samples were collected from the eye retro-orbital plexus of rats before and also at 0.5, 1, 2, 4, 6, 8 and 12 h after drug administration and the samples were analyzed for blood glucose by using glucose-oxidase/peroxidase method using a visible spectrophotometer. In long term study, the extract (300 mg/kg) was administered to streptozotocin-induced diabetic rats, daily for 8 weeks. Blood glucose was measured at weekly intervals for 4 weeks. Urine samples were collected before the induction of diabetes and at the end of 8 weeks of treatments and analyzed for urinary protein, albumin and creatinine levels. The data was compared statistically using one-way ANOVA with post-hoc Dunnet's t-test. RESULTS: The chloroform extract of T. chebula seeds produced dose-dependent reduction in blood glucose of diabetic rats and comparable with that of standard drug, glibenclamide in short term study. It also produced significant reduction in blood glucose in long term study. Significant renoprotective activity is observed in T. chebula treated rats. The results indicate a prolonged action in reduction of blood glucose by T. chebula and is probably mediated through enhanced secretion of insulin from the beta-cells of Langerhans or through extra pancreatic mechanism. The probable mechanism of potent renoprotective actions of T. chebula has to be evaluated. CONCLUSION: The present studies clearly indicated a significant antidiabetic and renoprotective effects with the chloroform extract of T. chebula and lend support for its traditional usage. Further investigations on identification of the active principles and their mode of action are needed to unravel the molecular mechanisms involved in the observed effects.

Animals↗

PubMed1979

Carcinogenicity of chloroform.

Chloroform is carcinogenic in rats, mice, and probably in dogs. Chloroform induced carcinomas of the liver and kidney and malignant tumors in other organs in rats and mice. Liver neoplasms have been described in three strains of mice. Carcinomas of the kidney were found in a first study in mice and in the repeat of that study. Dogs given chloroform developed neoplasms of the liver as well as in other organs. Rats given chloroform also developed toxic changes, particularly male rats, as a result of treatment. These lesions included interstitial fibrosis of the kidney; polyarteritis of the mesenteric, pancreatic, and other arterioles and arteries; and atrophy of the testes. These toxic changes may have interfered with the development of neoplasms in male rats.

Adenoma, Bile Duct↗

PubMed2003

Binding of the general anesthetics chloroform and 2,2,2-trichloroethanol to the hydrophobic core of a four-alpha-helix bundle proteins.

The structural features of general anesthetic binding sites on proteins are being examined using a defined model system consisting of a four-alpha-helix bundle scaffold with a hydrophobic core. Previous work suggested that halothane binding to the four-alpha-helix bundle was improved by (1) introducing a cavity into the hydrophobic core and (2) substituting a methionine side-chain in place of an alpha-helical heptad e position leucine. In this study, the ability of the general anesthetics chloroform and 2,2,2-trichloroethanol to bind to the hydrophobic core of the four-alpha-helix bundle (Aalpha2-L38M)2 is explored. The halogenated alkane chloroform binds with a dissociation constant (Kd) = 1.4 +/- 0.2 mM, whereas 2,2,2-trichloroethanol binds with a Kd = 19.5 +/- 1.2 mM. The affinity of both general anesthetics for the hydrophobic core of the four-alpha-helix bundle approximates their whole animal effective concentration in 50% of test subjects' (EC50) values, as shown previously for halothane. Tryptophan phosphorescence decay rates at 77 K are accelerated by a factor of 4.5 by both bound halothane and chloroform, indicating that the heavy-atom effect is responsible for a portion of the observed fluorescence quenching. Because heavy-atom effects are operative only at short distances, the findings indicate that these general anesthetics are binding in the vicinity of the indole rings of W15 in the hydrophobic core of the four-alpha-helix bundle scaffold. The results indicate that chloroform, halothane and 2,2,2-trichloroethanol may occupy the same sites on protein targets.

Amino Acid Sequence↗

PubMed1994

[Effect of chloroform on the extracting efficiency of adenosine tri-phosphate (ATP) from the cells of Mycobacterium leprae].

Effect of chloroform on the extraction of ATP from the cells of Mycobacterium leprae was investigated. The results demonstrate that the yields of ATP from the resting cells of M. leprae were much more higher when 100mM Tris-EDTA was added to the procedure than that of the routine method. The amounts of ATP extracted from the cells of M. leprae incubated either in 10% calf serum-buffer (pH 7) or 10% calf serum-2% glycerin-Dubos medium at 30 degrees C gradually increased with time of incubation when chloroform and 100mM-Tris-EDTA were used for extraction of ATP, whereas no increase and periodical decrease of ATP were observed when Tris-EDTA only without chloroform was used in the procedure of ATP extraction. Therefore, it is noted that the use of chloroform and 100mM-Tris EDTA is indispensable for extraction of ATP from the cells of M. leprae.

Adenosine Triphosphate↗

PubMed1998

Toxicity of chloroform.

(1) Chloroform is strongly absorbed by the pulmonary, oral and cutaneous routes. (2) It has adverse cardiac, hepatic, renal, dermatological, neurological and ophthalmological effects. Deaths related to chloroform use have occurred. In animals, chloroform is carcinogenic and embryotoxic. (3) Since 1997, the European and French medicines agencies have no longer considered chloroform to be a simple solvent. Only minimal amounts are authorised in drug preparations (no more than 0.6 mg/day).

Animals↗

PubMedDate not supplied

[Ether and chloroform narcosis in the pages of Zagreb newspapers from 1847 to 1849].

Overviews of the development of anesthesiology in Croatia always emphasize that the first report on the employment of ether anesthesia was published on March 13, 1847, in the Zadar newspaper Gazzeta di Zara. In the world as well, daily newspapers played an important part in spreading the news about the discovery and first use of ether anesthesia. This fact stimulated us to do a systematic search through Zagreb press of that time. Agramer Zeitung (Zagrebacke novine), with its supplement Luna--Beiblatt zur Agramer politischen Zeitung, then Narodne novine and Sudslavische Zeitung (Slavenski jug), were examined for the period from 1846 to the beginning of 1849. Research was directed to give the following answers: when the first writings about discovery and surgery in ether and chloroform anesthesia appeared, which primary and secondary sources of information were used; who wrote them; what kind of attitudes and opinions were promoted, and whose; and finally, did Zagreb newspapers communicate or record the news about first employment of ether and chloroform anesthesia in surgery in Croatia. Research results reveal that Zagreb press had an important role in informing Croatian public about breakthroughs and first experiences in the use of ether and chloroform anesthesia in Europe, and that it contributed to their popularization and employment in our settings. From January 26, 1847, Zagreb papers began publishing first articles about surgeries in ether anesthesia, referring to successes achieved in England and Scotland, and later in Vienna, Berlin, Prague and other big European towns. However, there were no reviews on first successes in America. Sources of information were mainly foreign daily papers, mostly Austrian, and much less often European professional medical journals. Zagreb papers did not report on first surgeries performed in Zadar, Dubrovnik and Split during 1847. The only news from the country referred to the procedure performed in August 1847 in Sisak. This is the first known published information about the beginnings of ether anesthesia in northwest Croatia. The article was written by an A. C., who witnessed and described first experiments using ether anesthesia in a Vienna clinic. Compared to the number of writings on ether anesthesia, introduction of chloroform received much less attention. The first news on Simpson's success was published on December 11, 1847. Regarding total number of texts dedicated to the topic of painless surgery, culmination was reached in 1847, and afterwards the interest of press in this field decreased. In the period from 1847 to the beginning of 1849, not one article was followed by subsequent comments of Croatian readers, either lay people or medical practitioners. Texts were not written sensationally, but with the aim to objectively inform the public by communicating experience and attitudes of contemporary reputable surgeons, including all professional details which might be useful for potential users--patients, as well as for Croatian physicians, surgeons, obstetricians, dentists and veterinarians.

Anesthesia, Inhalation↗

PubMed1975

[Swelling and loss of potassium in perfused livers following the influence of the vapours of carbon tetrachloride, chloroform and halothane on the perfusion medium (author's transl)].

Erythrocyte free perfused rat livers were treated with vaporous carbon tetrachloride, chloroform and halothane by equilibration in the oxygenator system. The potassium loss, the amount of swelling and the alteration of the perfusion rates were measured during the experiments as criteria of acute toxicity. In contrast to the well known behaviour of perfused livers during the intoxication with phalloidin the amount of liver swelling did not marekdly depend on the perfusion rates in acute CCl(4) poisoning. The mechanism of swelling must be different in both intoxications. Exposure of perfused livers to high concentrations of CCl(4) for several minutes only produced a marked K-+-loss within a short time. This injury could not be fully compensated after finishing the exposure. Dose response diagrams are presented for carbon tetrachloride, chloroform and halothane by use of the following criteria: potassium loss, swelling (increase of wet weight) and perfusion rates (ml.min-1.g-1). As total doses the amounts of solutes vaporized during the exposition were listed. In these diagrams chloroform appears to be more toxic than halothane. CCl4 occupies a middle position between chloroform and halothane. The course of dose response diagrams of halothane is different from those of CCl(4) and CHCl(3). The halothane diagrams increase critically at high doses, whereas the courves for CCl(4) and CHCl(3) rise continuously. With respect to effects on the hepatic microcirculation halothane seems to be less toxic than CCl(4). The results are discussed on the basis of the periods of exposition and the maximal concentrations of the solutes in the perfusion medium. With respect to these data CCl(4) is much more toxic than CHCl(3) and halothane. On the other hand there is no marked difference in acute hepatotoxicity between CHCl(3) and halothane.

Acute Disease↗

PubMedDate not supplied

[The morphine-scopolamine combination in chloroform anesthesia].

After introduction of surgical anesthesia with general agents such as ether and chloroform, a large number of deaths due to anesthetic toxicity were reported. With the aim to reduce toxicity several types of mixtures were devised. One of the most important was the association of opioids and scopolamine. This technique was compiled in a thesis on the use of morphine and scopolamine during anesthesia with chloroform which was presented by Dr. José Blasco Reta at the University of Madrid the 27th of June of 1907. Claude Bernard was the first to use this technique. He was based on the assumption that a previous injection of 1 cg of morphine acetate will decrease both, the needs and the risk of chloroform since this procedure shortened the excitation period, decreased ether-induced bronchial congestion, and prolonged for several hours the analgesic effect in the postoperative phase. The first who applied this technique in Spain was Dr. Losada, and Dr. Emilio Ruiz observed the rapid action of the mixture. After 1900, Schneiderlein added scopolamine in order to decrease the excitation and to reduce vomiting secondary to the association morphine-chloroform. Scopolamine was administered in 2 or 3 injections. Jun our country Dr. Lozano Monzón and Dr. Recasens used this pharmacologic association and considered it of beneficial effects when applied during labour. In a total number of 4,240 anesthetic procedures using the same technique, Dr. Blasco Reta reported 24 deaths, among them the first that occurred to Mr. Víctor Escribano between 1902 and 1903. Mortality was considered to be 1/1,000 cases.

Anesthesia↗

PubMed1989

[Study on quality of gossypol recrystalized from chloroform].

In this paper, the chemical properties of gossypol recrystalized from chloroform are described. Samples were dried at different temperatures at reduced pressure, and stored under room temperature for different times. They were identified and determined by melting point, thin layer chromatography, UV spectrophotometry, IR spectrophotometry, thermo-gravimetric analysis, X-ray diffraction, elementary analysis and also for the content of gossypol. The results of these tests proved gossypol to be solvated with chloroform at low temperature. This phenomenon decreased gradually with increase of drying temperature or storage time, and the content of gossypol increased accordingly. The presence of chloroform in the crystal interferes with the purity of gossypol. Thus, it is necessary to identify the presence of chloroform with oxygen flask ombustion-mercurimetry beforehand.

Chloroform↗

PubMed1978

[Effects of benzarone on the chloroform edema of the mouse and on the petechiae test in the guinea pig (author's transl)].

1. Chloroform edema. On the backskin of a mouse a wheal was produced by locally applied chloroform containing a fluid rich in protein. It was investigated whether a series of edema-protective drugs, i.e., drugs with anti-inflammatory effect, corticoids, and vascular-active drugs, could inhibit the development of the wheal edema. Only benzarone proved a statistically significant inhibition. The fact that other drugs proved less effective or not at all, could be based on the difference between the mechansim of the chloroform edema and that of other edema models. A reciprocal effect between benzarone and chloroform may be considered as well. 2. Petechiae test. A vitamin C-free nutrition over 3 weeks did not increase the "brittleness of capillaries" in the backskin of guinea pigs; whereas 50 mg benzarone/kg fed daily over a period of 3 weeks caused a significant decrease in the number of petechiae compared to that in the controls. This effect, most likely, was not due to an improved stability of the capillaries but was based on the reduced blood circulation of the skin.

Animals↗

PubMed1977

Reduction of nitro-BT by various chloroform-methanol fractions obtained from the grey matter of the rat brain.

Histochemical studies have shown, that nerve fibers can not be visualised in the grey matter of the brain by the reduction of Nitro-BT, if prior to incubation an extraction with chloroform-methanol of the brain slices was performed. According with this finding the grey matter of the rat brain was homogenized and extracted with chloroform-methanol. After centrifugation the obtained supernatant was three times evaporated. Each time before evaporation the supernatant was dissolved in chloroform-methanol solution v/v 2:1. The substance obtained was of teer-like consistency and brown colour. The substance was weight and used for further experiments. Similar extraction was done with phosphate buffer. It was found, that the phosphate buffer does not extract the searched for substance. The comparison of the extinction curves of various fractions has shown that the highest concentration of the substance which reduces Nitro-BT can be found in that fraction which was three times washed with chloroform-methanol. The same concentration was observed in the water fraction which was the result of purification with hexanmethanol. From our investigations it may be concluded that the substance which reduces Nitro-BT in tissue is bound with lipids and purified form lipids passes into water.

Animals↗

PubMed1993

Hepatic or pulmonary ornithine decarboxylase and vitamin A status in Wistar rat, enzyme kinetics--influence of chloroform.

The ODC activity, initial enzyme in the polyamines synthesis, was studied in the liver and lungs of Wistar rat under avitaminosis A. In the liver: ODC activity is decreased by vitamin A deficiency but partially recovered with retinol repletion during 2 weeks. An intraperitoneal injection of chloroform markedly stimulates the ODC activity, as in the deficient rat as in the normal animal; the response following stimulation is even relatively higher under avitaminosis A. The Km value of ODC increases in the deficiency; intermediate values are obtained in retinol repletion. However the chloroform injection has no effect on the Km values under any of the nutritional state. In the lungs: The baseline ODC activity is slightly decreased in the deficient animals. The chloroform stimulation induced relatively a moderate increase in the normal rat (2 fold over baseline level); it is more intense (4 fold) in deficient animal and the ODC activity is well above those of normally fed control in absolute value. As in the liver, the enzyme Km increases in avitaminosis A and a retinol repletion partially attenuates this influence. Here again, the chloroform stimulation has no effect on the Km values.

Animals↗

PubMed1993

[Chloroform-induced hepatic injury: a case report].

Chemical hepatic injury is not rare in Taiwan. We here report such an injury induced by chloroform. A previously healthy 26-year-old married woman was admitted under the impression of acute chemical hepatitis in December, 1991. Two weeks before, she had used chloroform as glue to unite two pieces of plastic pencil sharpener at home. Nasty odor was sensed while working. After series of hepatitis workup, liver echo, site visit, survey of coworkers and gas chromatography for the "glue", the diagnosis of chloroform-induced hepatic injury was confirmed. This case found that neither employer nor employee was aware of the toxicity of chloroform. No ventilation system or personal respiratory protection equipment was provided. Preemployment training and Material Safety Data Sheet were obviously insufficient, also. The diagnostic criteria of chemical hepatic injury were therefore proposed to alert medical professionals, industrial hygienist, safety personnel and factory inspectors, not to prompt an early diagnosis but also hopefully to prevent the occurrence of occupational liver diseases.

Adult↗

PubMed1977

The quantitative assay of 3-hydroxy-3-methylglutaryl coenzyme A reductase: comparison of a thin-layer chromatographic assay with a rapid chloroform extraction assay.

Two assays for the quantitative measurement of HMG-CoA reductase, the major regulatory enzyme in hepatic cholesterol biosynthesis, are described. The first of these procedures employs thin-layer chromatography (TLC) of the reaction product on plastic-backed silica gel G strips impregnated with ammonium carbonate. The TLC strip is then cut into 14 segments and each segment is assayed for radioactivity. Extraction efficiency and exact chromatographic mobility are monitored by the use of authentic [4-(3)H]mevalonolactone as an internal reference. A wide and complete separation is achieved between HMG and mevalonolactone. Also the radiochemical purity of biosynthetic [3-(14)C]mevalonolactone can be assessed by measurement of the (3)H/(14)C ratio across the mevalonolactone peak. While the TLC assay is accurate and sensitive, it is laborious. Therefore a second assay procedure was developed using chloroform extraction of an incubation mixture saturated with solid equal molar KH(2)PO(4)-K(2)HPO(4) at pH 6.8. Extraction efficiency was monitored by the addition of authentic [4-(3)H]mevalonolactone as an internal reference. The chloroform assay procedure was compared with the TLC procedure over a wide range of enzyme activities, both for rat liver microsomal HMG-CoA reductase and for solubilized enzyme. Excellent correspondence (r = 0.999) between the two assays was observed. TLC performed on the chloroform extract demonstrated that biosynthetic [3-(14)C]mevalonolactone was the only (14)C-labeled compound present in the extract. The chloroform extraction assay is rapid; 20-30 samples can be processed in 2-3 hr. This procedure should facilitate studies concerning the nature and regulation of HMG-CoA reductase.

Alcohol Oxidoreductases↗

PubMed1996

Two fatal cases of dichloromethane or chloroform poisoning.

The two cases presented here involve deaths that were due to dichloromethane or chloroform poisoning. The dichloromethane and chloroform were determined in biological specimens by headspace gas chromatography with mass spectrometric detector. In one case, dichloromethane concentrations found were 252 mg/L (blood), 75 mg/kg (brain) and 30 mg/kg (heart). From the case investigation, it was determined that the death was accidental but related to the dichloromethane poisoning. In the other case, chloroform concentrations were 60 mg/kg (blood) and 14 mg/kg (lungs), respectively. This case, the cause of death was chloroform poisoning by forced inhalation in addition to oronasal obstruction.

Adult↗