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Biomedical subjects

D Henschler

Publications and source records attributed to D Henschler.

At least 127 records · Page 7Linked to original sources
PubMed1977

Carcinogenicity of trichloroethylene: fact or artifact?

Technical trichloroethylene has been found carcinogenic in mice after high daily doses per os. A GC-MS analysis of this technical sample revealed the presence of considerable amounts of epichlorohydrin and 1.2-epoxibutane as stabilizers. These epoxides are highly mutagenic in the Ames test and are, most probably, responsible for the carcinogenic effect found in mice. The question whether trichloroethylene is carcinogenic or not remains open.

Carcinogens↗
PubMed1977

Spectral evidence for 2,2,3-trichloro-oxirane formation during microsomal trichloroethylene oxidation.

During aerobic incubation of trichloroethylene with rabbit liver microsomes and NADPH a difference absorption peak appears at 451-452 nm. Trichloroethylene does not form a ligand absorption spectrum with hepatic microsomes reduced by dithionite, or in anaerobic incubates in the presence of NADPH. Addition of trichloroethylene epoxide (2,2,3-trichloro-oxirane) to reduced suspensions of rabbit liver microsomes produces high difference absorption at 452 nm, the optical Ks being approximately 2 mM. Of all possible metabolites of trichloroethylene only trichloroethanol forms absorption in the vicinity of 480 nm, and the broad absorption band reveals relatively low absorption near 450 nm. Dichloroacetyl chloride is the main thermal rearrangement product of trichloroethylene epoxide, and also produces 452 nm absorption in reduced microsomes. However, the difference absorption is 5 times smaller than the absorption produced by the intermediate formed during incubation of trichloroethylene in metabolising liver microsomes. These observations include strong evidence for epoxide formation during microsomal oxidation of trichloroethylene. 14C-labelled trichloroethylene binds irreversibly to hepatic macromolecules in vivo and in vitro. Possible rearrangement pathways of 2,2,3-trichloro-oxirane and reactive intermediates are presented.

Animals↗
PubMed1977

Metabolism and mutagenicity of halogenated olefins--a comparison of structure and activity.

Chlorinated ethylenes are metabolized in mammals, as a first step, to epoxides. The fate of these electrophilic intermediates may be reaction with nucleophiles (alkylation), hydrolysis, or intramolecular rearrangement. The latter reaction has been studied in the whole series of chlorinated epoxiethanes. The rearrangement products found were: acyl chlorides (tetrachloro-, trichloro-, and 1,1-dichloroethylenes), or chlorinated aldehydes (1,2-dichloroethylenes, cis- and trans-, vinyl chloride). The metabolities found in vivo are identical with, or further derivatives of these rearrangment products, with one important exception: trichloroethylene. With this compound, in vivo rearrangement yields chloral exclusively. The mechanism of the different rearrangement has been identified as a Lewis acid catalysis. All chlorinated ethylenes have been investigated in a tissue-mediated mutagenicity testing system. The prominent molecular feature of those with mutagenic effects (trichloro-, 1,1-dichloro-, and monochloroethylene) is unsymmetric chlorine substitution which renders the epoxides unstable, whereas symmetric substitution confers relative stability and nonmutagenic property.

Animals↗
PubMed1977

[Bioavailability of fluorides from various salts and from various dietary components].

In six male subjects fluoride bio-availability after oral application of NaF and MgF2 was examined and the influence of food on fluoride absorption was studied by recording fluoride level in plasma and parotid saliva for 24 hours. In addition, fluoride profiles in the plasma of four beagle dogs after the intake of fluoride as NaF, MgF2 and CaF2 with and without addition of milk and dairy products were established. There were great differences in extent and speed of absorption among the different preparations some of which were demonstrated not to release fluoride at all. As was expected, absorption was quicker and more complete in patients with empty stomach than with simultaneous food intake. Milk and dairy products delay fluoride uptake without considerably reducing the overally amount of fluoride resorption.

Adult↗
PubMed1977

[Activation mechanisms in chlorinated aliphatic compounds/experimental possibilities and clinical significance (author's transl)].

Chemical reactivity, biotransformation and toxic effects of chlorinated aliphatic compounds are decisively determined by type and number of chlorine substitutions. In saturated compounds, chlorine substitution exerts a destabilization; metabolic reactions are free radical formation and dechlorination or dehydrochlorination, respectively, under formation of olefins. In saturated alkenes, Cl-substitution leads to a stabilization of the olefinic double bond. Biotransformation of this class of compounds starts with epoxidation. The epoxides are prone, among other reactions, to intramolecular rearrangement; more stable aldehydes or acid chlorides are formed. In the series of chlorinated ethylenes, the rearrangement mechanisms have been studied systematically in vitro and in vivo. As judged from the identified metabolites there is accordance in vitro and in vivo, with one important exception: trichloroethylene. The only formation of chloral in vivo may be due to a catalysis by the iron in P450. In a modified Ames test system the unsymmetrically substituted chlorinated ethylenes are found mutagenic (tri-,1,1-dichloroethylene and vinyl chloride), whereas symmetrically substituted molecules are inactive. The reason for this is seen in the high instability of the unsymmetric molecules caused by the electron withdrawal effect of chlorine.

Animals↗
PubMed1976

Neurotoxic effects of dichloroacetylene.

In inhalation tests involving lethal as well as sublethal doses of dias examined in rabbits by means ofhistologic and neurofunctional methods. Histologic examination revealed chromatolysis, disintegration of Nissl bodies, and cell shrinkage in proportion to the doses employed in the nuclei of the unpaired brain stem, in the sensory cortical regions and especially in the sensory cranial nerve nuclei. The sensory trigeminal nucleus was involved most severely, followed in decreasing intensity 0y the facial and oculomotor nerves and the motor trigeminal nucleus; the least changes were observed in the acoustic nerve. By testing the protopathic sensitivity of the facial skin it was possible for the first time to produce evidence of a sensory loss in the distribution of the trigeminal nerve by animal experimentation. The neuropathological and functional deficits observed may explain the cranial nerve lesions in human DCA intoxication; however, these lesions seem to be less distinct in experimental animals.

Acetylene↗
PubMed1976

Carcinogenic potential of chlorinated ethylenes tentative molecular rules.

Chlorinated ethylenes are activated in mammalian metabolism to oxiranes. Only those with asymmetric chlorine substitution are mutagenic (trichloroethylene, vinylidence chloride and vinyl chloride) whilst the symetric molecules (tetrachloroethylene, cis- and trans-1.2-dichloroethylene) are inactive in this respect. Thus, stability of the oxirances (higher in the symmetric molecules, lower in the asymmetric ones) seems to be the important feature for the mutagenic, and possibly carcinogenic potential.

Carcinogens↗
PubMed1975

Metabolism of trichloroethylene in man. III. Interaction of trichloroethylene and ethanol.

Volunteers inhaled a constant concentration of 50 ppm trichloroethylene (Tri) for 6 hrs per day on 5 consecutive days. Simultaneous ethanol (EtOH) ingestion (blood level 0.6%) inhibits the metabolization of Tri to trichloroethanol (TCE) and trichloroacetic acid (TCA) by 40% on the average. Oxidation of Tri to TCA does not occur as long as EtOH is present. During this time period the blood Tri-concentration increases 2 1/2-fold, that in the expired air rising 4-fold, as compared to Tri inhalation without EtOH. TCE glucuronidation is not subject to inhibition. On concurrent inhalation of Tri, the EtOH and acetaldehyde levels are slightly increased over the control values without Tri. The mechanisms underlying the alternate inhibition of mixed-function oxygenases and aldehyde dehydrogenase on simultaneous intake of Tri and EtOH are discussed. The intolerance reaction occurring on combined exposure to Tri and EtOH can be interpreted as an accumulation of Tri in the CNS resulting from the complete depression of Tri oxidation.

Acetaldehyde↗