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D Henschler

Publications and source records attributed to D Henschler.

At least 109 records · Page 6Linked to original sources
PubMed1980

[Acetone].

Explore the source record for details and available documents.

Acetone↗
PubMed1980

Prodrugs of etilefrine: synthesis and evaluation of 3'-(O-acyl) derivatives.

A series of 3'-(O-acyl) derivatives of etilefrine (alpha-[(ethylamino)methyl]-3'-hydroxybenzyl alcohol) was synthesized. Correlations between structure and solubility, pKa value, lipophilicity, and esterase-catalyzed hydrolysis were demonstrated. Of special interest is the 3'-(O-pivaloyl) derivative, which shows, in addition to favorable solubility and improved lipophilicity, marked stability against enzymatic cleavage in blood along with a high rate of hydrolysis in the liver.

Animals↗
PubMed1980

Carcinogenicity study of trichloroethylene by longterm inhalation in three animal species.

Pure trichloroethylene (tri), stabilized by an amine base, was administered by inhalation at 0, 100, and 500 ppm for 6 h/day, 5 days/week, for 18 months to mice, rats and Syrian hamsters of both sexes. No significant increase in tumor formation was observed in any species or dosing group, except in malignant lymphomas, which were increased in female mice in the following incidence rates: 9/29 (controls), 17/30 (100 ppm), and 18/28 (500 ppm). Whether or not this high occurrence of lymphomas, which is peculiar to this strain of mice (NMRI) has any relationship to tri-exposure, cannot be decided upon by the present experiment. It is concluded that from these findings no indication for a carcinogenic potential of pure trichloroethylene can be deduced.

Animals↗
PubMed1980

Identification of potential carcinogens in technical grade 1,1,1-trichloroethane.

Gas chromatography and gas chromatography-mass spectrometry were employed to analyze 22 samples of technical grade 1,1,1-trichloroethane for impurities. Eighteen contained vinylidene chloride (1,1-dichloroethylene) (30-900 micrograms/ml) and further contaminants were identified as 1,1-dichloroethane (11), trichloroethylene (12), and 1,1,2-trichloroethane (9). Nitromethane (18), 1,2-epoxybutane (19), tert. butanol (7), and dioxane (10) were detected as stabilizers. It is recommended that the manufacturers should eliminate vinylidene chloride and stabilizers which carry a carcinogenic and/or mutagenic risk, from technical samples of 1,1,1-trichloroethane.

Animals↗
PubMed1980

Decomposition of the neuro- and nephrotoxic compound dichloroacetylene in the presence of oxygen: separation and identification of novel products.

Dichloroacetylene (DCA) shows pronounced nephrotoxic effects in several animal species and is neurotoxic in humans. It is a chemically highly reactive compound that decomposes spontaneously in the presence of oxygen. The chemical decomposition of DCA has been studied in order to understand the role of the decomposition products for the toxic effects of DCA. Seven compounds were identified by their mass spectra and by comparison with authentic reference materials. Among these were phosgene, hexachlorobutadiene, and other reactive products (e.g., trichloroacetyl chloride and trichloroacryloyl chloride), which may explain, in part, the toxicity of DCA.

Acetylene↗
PubMed1979

Molecular mechanism of 1,1-dichloroethylene toxicity: excreted metabolites reveal different pathways of reactive intermediates.

The excretion and biotransformation of [14C] 1,1-dichloroethylene (vinylidene chloride, VDC) after administration of a single oral dose has been investigated in female rats. Seventy-two hours after a dose of 0.5, 5.0, and 50.0 mg/kg, 1.26, 9.70, 16.47%, respectively, are exhaled as unchanged VDC, and 13.64, 11.35, 6.13% as 14CO2. The main pathway of elimination is through renal excretion with 43.55, 53.88, 42.11% of the administered radioactivity. Through the biliary system, 15.74, 14.54, 7.65% of the activity are eliminated. The isolation of the main metabolites of VDC from 24 h urine is accomplished through the combined application of solvent extraction, ion exchange chromatography and thin layer chromatography. Then gas chromatography and mass spectrometry are used for their identification. Three metabolites have been identified: thiodiglycolic acid, N-acetyl-S-(2-carboxymethyl)cysteine and methyl-thio-acetylaminoethanol. In addition, three smaller unidentified radioactive peaks have been found. Thiodiglycolic acid is the main metabolite in VDC metabolism. The simultaneous formation of an ethanolamine- and a cysteine-conjugation product points to different reaction pathways of the postulated intermediate reactive epoxide; ethanolamine probably originates from membrane lipids, which react with VDC-epoxide and/or its derivatives. This pathway could explain, in part, the parenchyma damaging effect of VDC.

Administration, Oral↗
PubMed1978

Role of liver glutathione in 1,1-dichloroethylene metabolism and hepatotoxicity in intact rats and isolated perfused rat liver.

The liver glutathione content was measured after oral administration of 1,1-dichloroethylene (vinylidene chloride = VDC; dissolved in olive oil) and its significance for the metabolism and hepatotoxicity of VDC was investigated. After treatment with 1000 mg/kg VDC p.o., glutathione decreased to 33% of the control values within 4 h but returned to the control level after 24 h. An identical fall in glutathione after VDC administration was found to occur in animals which had been fasted for 18 h. In these animals the baseline values of glutathione were lowered by 21%. The depletion of glutathione was dependent on the dosage of VDC. The conversion rate of VDC by the isolated perfused livers was 7.64 mumoles/g liver after 3 h-perfusion, if 5000 ppm of VDC were supplied in the gas phase. Lowering the glutathione content to 15% of the normal value (by diethylmaleate, 25 mumoles added directly to the perfusate) resulted in a reduction of VDC conversion by 18%. Furthermore the viability (with the lactate/pyruvate ratio serving as the parameter) of the liver was distinctly depresesd. No effect on viability nor on metabolization rate was noted when perfusing the livers of 18-h fasted animals. The concentrations of the glutamate-oxaloacetate transaminase (SGOT) and glutamate-pyruvate transaminase (SGPT) in the perfusate failed to show an increase. These findings indicate that there is no correlation between the liver glutathione level and the increased lethality of VDC in fasted rats.

Animals↗
PubMed1977

Metabolic activation of chlorinated ethylenes: dependence of mutagenic effect on electrophilic reactivity of the metabolically formed epoxides.

In chlorinated ethylenes, the chlorine substitution exerts, by its electron withdrawal effect, a stabilization of the molecule which increases with the number auf chlorine residues. All chlorinated ethylenes are metabolically transformed, in a first step reaction, to epoxides which may rearrange to aldehydes or acyl chlorides, respectively, undergo hydrolysis to diols, conjugate with glutathione, or react, by alkylation, with cellular macromolecules. The electrophilicity of the epoxides is high with those having an unsymmetric chlorine substitution, and comparatively low with the others bearing symmetric chlorine residues. According to in vitro mutagenicity testing in a modified Ames system, the following rule on structure/activity-relationship has been worked out: mutagenic potential is bound to unsymmetric substitution and high chemical reactivity (as with vinyl chloride, vinylidene chloride, and trichloroethylene), symmetric substitution results in lower chemical reactivity and non-mutagenicity. So far, the rule is substantiated by positive carcinogenic effects in animal experiments with vinyl chloride, vinylidene chloride and trichloroethylene.

Biotransformation↗