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A Buchter

Publications and source records attributed to A Buchter.

27 records · Page 2Linked to original sources

Pharmacokinetics of vinyl chloride in the rat.

When rats are exposed to [14C]vinyl chloride in a closed system, the vinyl chloride present in the atmosphere equilibrates with the animals' organism within 15 min. The course of equilibration could be determined using rats which had been given 6-nitro-1,2,3-benzothiadiazole. This compound completely blocks metabolism of vinyl chloride. The enzymes responsible for metabolism of vinyl chloride are saturated at an atmospheric concentration of vinyl chloride of 250 ppm. Pharmacokinetic analysis shows that no significant cumulation of vinyl chloride or its major metabolites is to be expected on repeated administration of vinyl chlorides. This may be consistent with the theory that a reactive, shortly living, metabolite which occurs in low concentration only, may be responsible for the toxic effects of vinyl chloride.

Animals↗

Metabolism of 14 C-vinyl chloride in vitro and in vivo.

Rat liver microsomes metabolise 14 C-vinyl chloride to intermediates which irreversibly bind to the microsomal protein and to soluble proteins and RNA, when these compounds are added to the incubation. A superoxide (O2) generating system comprised of phenazine methosulfate and NADH also converts 14 C-vinyl chloride to metabolites which irreversibly bind to albumin. These data are consistent with the assumption of chloroethylene oxide being the primary reactive metabolite of vinyl chloride. If rats are exposed to 14 C-vinyl chloride, about half of the radioactive metabolites in the liver microsomal fraction is bound irreversibly to microsomal protein, when assessed immediately after exposure. Large amounts of polar, extractable, metabolites are present in the cytosol fraction. The amount of radioactivity in tissues of the rats, irreversibly bound immediately after exposure, comprises 10 - 40% of the total radioactivity in tissues. This percentage rises up to 70% after 48 hrs. Som radioactivity derived from 14 C-vinyl chloride is also incorporated into DNA and RNA of liver. Whereas the peak of incorporation of 14 C into DNA is already reached immediately after exposure to 14 C-vinyl chloride, specific labelling of RNA increases after exposure until its maximum after 24 hours.

Albumins↗

Clinical toxicology of acrylonitrile.

Acrylonitrile monomer is used in the production of artificial fibres and resins. It has been used as a fumigant. Acrylonitrile has acute toxic effects for men and animals on over-exposure by inhalation of the vapor, dermal absorption of the liquid and oral intake. Symptoms in men are non-specific and predominantly related to the central nervous system, the respiratory tract, the skin and to the gastrointestinal tract. Severe acrylonitrile intoxication is followed by loss of consciousness, convulsions, respiratory arrest and death. The detailed investigation of a patient with complaints after chronic exposure demonstrates the necessity of objective neurophysiologic studies. Acrylonitrile has carcinogenic properties in animals. It is also embryotoxic and teratogenic. Epidemiological studies in men exposed to acrylonitrile are not convincing. There may be a slight excess of deaths from lung cancers and other malignant tumors. Effects of potential antidotes were studied in animal experiments. Rats were intoxicated with lethal doses of acrylonitrile by different routes of application. The cyanide antidotes 4-dimethylaminophenol plus thiosulfate showed some protective effect only after oral but not after i.p. or inhalational acrylonitrile administration. Of the sulfhydryl compounds cysteine, N-acetyl-cysteine, cysteamine and diethyldithiocarbamate, the two antidotes cysteine and N-acetylcysteine proved to be especially effective. From these experiments a tentative schedule of antidotal therapy for humans accidentally intoxicated with acrylonitrile is inferred, using N-acetylcysteine by analogy with the therapeutic regimen effective in cases of paracetamol poisoning.

Acrylonitrile↗