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N-acetyl-cystein als antidot bei akzidenteller acrylnitril-intoxikation

N-acetyl-cysteine as an antidote in accidental acrylonitrile intoxications

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Summary

Acute acrylonitrile intoxications are followed by loss of consciousness, convulsions, respiratory arrest, and may end fatally. Common cyanide antidotes have not proved to be effective. In previous animal experiments we could demonstrate that the cyanide antidotes show some protective effect only after oral acrylonitrile application. Only a minimal amount of inhaled acrylonitrile will be transformed into cyanide, in contrast to pharmacokinetics after oral intake. After acrylonitrile inhalation the toxic effect of the whole molecule (cyanethylation) is important, and sulfhydryl compounds show antidotal effects. Further animal experiments demonstrate the superior antidotal effects of N-acetyl-cysteine after acrylonitrile inhalation. Intravenous injection of N-acetyl-cysteine in high doses is recommended according to the treatment of paracetamol poisoning.

Zusammenfassung

Akute Acrylnitril-Intoxikationen können mit Bewußtlosigkeit, Krämpfen und Atemstillstand zum Tode führen. Die gebräuchlichen Cyanid-Antidote haben sich hierbei als nicht ausreichend effektiv erwiesen. In früheren Tierversuchen konnten wir zeigen, daß die Cyanid-Antidote nur bei der oralen Acrylnitril-Intoxikation einen therapeutischen Wert haben. Die Cyanid-Abspaltung ist bei der inhalativen Acrylnitril-Vergiftung nur gering, im Gegensatz zur oralen Intoxikation. Bei der Acrylnitril Inhalation steht die toxische Wirkung des Gesamtmoleküls (Cyanethylierung) im Vordergrund. Als Antidote haben sich hier thiolhaltige Substanzen als effektiv erwiesen. In weiteren Tierversuchen wird gezeigt, daß N-Acetyl-Cystein das überlegene Antidot bei der inhalativen Acrylnitril-Intoxikation ist. Aufgrund der Erfahrungen mit der Injektion von hohen Dosen N-Acetyl-Cystein bei der Paracetamol-Intoxikation wird ein entsprechendes Therapieschema empfohlen.

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Literatur

  • Ageeva TS (1970) The condition of the metabolism of mediating substances in workers producing acrylonitrile (russ). Tr Sarat Med Inst 78:10–13

    Google Scholar 

  • Alsop JA (1977) Use of acetylcysteine in acetaminophen poisoning. Hosp Pharmacy 12:493–497

    Google Scholar 

  • American Conference of Governmental Industrial Hygienists: Documentation of the Treshold Limit Values 1980, Suppl 1981, 1982. ACGIH, 6500 Glenway Ave, Cincinnati, OH 45211

    Google Scholar 

  • American Conference of Governmental Industrial Hygienists: Threshold Limit Values for Chemical Substances and Physical Agents in the Work Environment, 1982. ACGIH, 6500 Glenway Ave, Cincinnati, OH 45211

    Google Scholar 

  • Appel KE, Peter H, Bolt HM (1981a) Effect of potential antidotes on the acute toxicity of acrylonitrile. Int Arch Occup Environ Health 49:157–163

    Google Scholar 

  • Appel KE, Peter H, Bolt HM (1981b) Interaction of acrylonitrile with hepatic microsomes of rats and men. Toxicol Lett 7:335–340

    Google Scholar 

  • Berufsgenossenschaft der chemischen Industrie: Merkblatt „Acrylnitril”, Ausgabe 10 (1980). Verlag Chemie, Weinheim

    Google Scholar 

  • Berufsgenossenschaft der chemischen Industrie: Acrylnitril, Merkblatt M 016 5 (1983). Jedermann-Verlag, Dr. O. Pfeffer, Heidelberg

    Google Scholar 

  • Bondarev GI, Stasenkova KP, Vissarionova VJA (1976) Protective action of sulfur-containing compounds in acrylonitrile poisoning. Vopr Pitan 4:55–58 [Moskva]

    Google Scholar 

  • Bondarev GI, Stasenkova KP (1977) Experimental evaluation of a therapeutic-prophylactic nutrition in exposure to acrylonitrile. Vopr Pitan 5:78–82 [Moskva]

    Google Scholar 

  • Buchter A, Peter H (1983) Clinical toxicology of acrylonitrile. J Ital Med Lavoro [im Druck]

  • Buchter A, Peter H, Appel KE, Bolt HM (1981) Grundlagen der Toxizität von Acrylnitril und der Behandlung akuter Acrylnitril-Vergiftungen. Verh Dtsch Ges Arbeitsmed 21:205–208

    Google Scholar 

  • Buchter A, Peter H, Bolt HM (1982) Zur Toxikologie von Acrylnitril. Verh Dtsch Ges Arbeitsmed 22:183–185

    Google Scholar 

  • Deutsche Forschungsgemeinschaft: Maximale Arbeitsplatzkonzentrationen und Biologische Arbeitsstofftoleranzwerte 1982. Senatskommission zur Prüfung gesundheitsschädlicher Arbeitsstoffe. Verlag Chemie, Weinheim

  • Grahl R (1970) Toxikologie und Wirkungsweise von Acrylnitril. Zentralbl Arbeitsmed 12: 369–378

    Google Scholar 

  • Gut I, Nerudová J, Kopecký J, Holeček V (1975) Acrylonitrile biotransformation in rats, mice and chinese hamsters as influenced by the route of administration and by phenobarbital, SKF 525 A, cysteine, dimercaprol, or thiosulfate. Arch Toxicol 33:151–161

    Google Scholar 

  • Hashimoto K, Kani R (1965) Studies on the toxicology of acrylonitrile. J Ind Health 3:30–46

    Google Scholar 

  • Holeček V, Kopecky J (1981) Conjugation of glutathione with acrylonitrile and glycidonitrile. In: Gut J, Cikrt M, Plaa GL (eds) Industrial and environmental xenobiotics. Springer, Berlin Heidelberg New York Tokyo, pp 238–244

    Google Scholar 

  • Henschler D Gesundheitsschädliche Arbeitsstoffe. Toxikologisch-arbeitsmedizinische Begründung von MAK-Werten. Verlag Chemie, Weinheim, 1.-8. Lieferung, 1972-1981

    Google Scholar 

  • IARC: Acrylonitrile, acrylic and modacrylic fibers, and acrylonitrile-butadiene-styrene and styrene-acrylonitrile copolymers. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, vol 19, 1979

  • Lyons L, Studdiford JS, Sommaripa AM (1977) Treatment of acetaminophen overdosage with N-acetylcysteine. New Engl J Med 296:174–175

    Google Scholar 

  • McLaughlin M, Krivanek ND, Trochimowicz HJ (1976) Evaluation of antidotes for acrylonitrile poisoning. Toxicol Appl Pharmacol 37:133–134

    Google Scholar 

  • Oh TE, Shenfield GM (1980) Intravenous N-acetylcysteine for paracetamol poisoning. Med Journ Australia 1:664–665

    Google Scholar 

  • Paulet G, Desnos I (1961) L'acrylonitrile toxicité — méchanisme d'action therápeutique. Arch Int Pharmacodyn 131:54–83

    Google Scholar 

  • Peter H, Bolt HM (1981) Irreversible protein binding of acrylonitrile. Xenobiotica 11:51–56

    Google Scholar 

  • Peter H, Schwarz M, Mathiasch B, Appel KE, Bolt HM (1983a) A note on synthesis and reactivity towards DNA of glycionitrile, the epoxide of acrylonitrile [short communication]. Carcinogenesis 4:235–237

    Google Scholar 

  • Peter H, Appel KE, Berg R, Bolt HM (1983b) Irreversible binding of acrylonitrile to nucleic acids. Xenobiotica 13:19–25

    Google Scholar 

  • Peter H (1983c) To the biochemistry, carcinogenic effect and toxicology of the plastic monomer acrylonitrile. Dissertation at the University of Mainz (FRG) Dept of Chemistry

  • Peter H, Buchter A, Trampert M, Bolt HM (1983d) Untersuchungen zu ersten medizinischen Maßnahmen bei akuter Vergiftung mit Acrylnitril. Verh Dtsch Ges Arbeitsmed 23 [im Druck]

  • Peter H, Bolt HM (1983e) Experimental pharmacokinetics and toxicology of acrylonitrile. J Ital Med Lavoro [im Druck]

  • Peterson RG, Rumack BH (1977) Treating acute acetaminophen poisoning with acetylcysteine. Jama 22, vol 237:2406–2407

    Google Scholar 

  • Pflüger K-H (1980) Toxikologie und Therapie der Paracetamol-Vergiftung. Internist 21:735–738

    Google Scholar 

  • Prescott LF (1981) Treatment of severe acetaminophen poisoning with intravenous acetyl-cysteine. Arch Int Med 141:

  • Prescott LF, Park J, Ballantyne A, Adriaenssens P (1977) Treatment of paracetamol (acetaminophen) poisoning with N-acetylcysteine. Lancet 2:432–434

    Google Scholar 

  • Prescott LF, Illingworth RN, Critchley JA, Stewaet MJ, Adam RD, Proudfoot AT (1979) Intravenous N-acetylcysteine: The treatment of choice for paracetamol poisoning. Br Med J 2:1097–1100

    Google Scholar 

  • Rumack BH, Peterson RG (1978) Acetaminophen overdose: Incidence, diagnosis, and management in 416 patients. Pediatrics [Suppl] 62:898–903

    Google Scholar 

  • Sheffner AL, Medler EM, Bailey KR, Galeo DG, Mueller AJ, Sarret MP (1966) Metabolic studies with acetylcysteine. Biochem Pharmacol 15:1523–1535

    Google Scholar 

  • Silver EH, Kuttab SH, Hassan T, Hassan M (1982) Structural consideration in the metabolism of nitriles to cyanide in vivo. Drug Metab Disp 10:495–498

    Google Scholar 

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Authors and Affiliations

  1. Institut und Poliklinik für Arbeits- und Sozialmedizin der Universität zu Köln, Joseph-Stelzmann-Straße 9, D-5000, Köln 41

    A. Buchter

  2. Institut für Arbeitsphysiologie an der Universität Dortmund, Abteilung Toxikologie und Arbeitsmedizin, D-4600, Dortmund, Bundesrepublik Deutschland

    H. Peter & H. M. Bolt

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  1. A. Buchter
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  2. H. Peter
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  3. H. M. Bolt
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Buchter, A., Peter, H. & Bolt, H.M. N-acetyl-cystein als antidot bei akzidenteller acrylnitril-intoxikation. Int. Arch Occup Environ Heath 53, 311–319 (1984). https://doi.org/10.1007/BF00380670

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  • DOI: https://doi.org/10.1007/BF00380670

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