Abstract
1-14C-Acrylonitrile (VCN) was given orally to rats, 27% of the given dose was excreted in bile in 6 h. When 1-14C-VCN was given to overnight fasted or cobaltous chloride treated rats, a significant increase in the biliary excretion occurred. Pretreatment of rats with phenobarbital produced no change, while diethyl maleate pretreatment significantly decreased the portion of the dose excreted in bile in 6 h. Four metabolites of 1-14C-VCN have been isolated from the collected bile, and characterized. The two major biliary metabolites were found to be glutathione (GSH) conjugates of VCN, indicating the importance of GSH in VCN biotransformation.
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Abreu MA, Ahmed AE (1980) Metabolism of acrylonitrile to cyanide — in vitro studies. Drug Metab Dispos 8: 376–379
Anonymous Federal Registry, October 1979 and NIOSH Report, DHEN(NIOSH) publication number 78–116, U.S. Government Printing Office
Benke B, Ferenczi R, Kovacs K (1974) A new acid hydrolysis method for determining Tryptophan in peptides and proteins. Anal Biochem 60: 45–50
Boyland E, Chasseaud LF (1967) Enzyme catalysed conjugations of glutathion with carbonyl compounds. Biochem J 104: 95–102
Boyland E, Chasseaud LF (1968) Enzymes catalysing conjugations of glutathione with α.β-unsaturated carbonyl compounds. Biochem J 109: 651–661
Cantrell ET, Marshall M, Mclemore T, Ghanayem B, Busbee D (1979) Secondary metabolism of Benzo(a)pyrene in human cells. Proc West Pharmacol Soc 22: 273–276
Fairchild EJ, Lewis RJ, Taken RL (eds) (1977) Registry of toxic effects of chemical substances, U.S. Department of Health, Education, and Welfare; Nat. Institute of Occupational Safety and Health; Rockville, MD, pp 31–38
Gut I, Cirkt M, Plaa GL (eds) (1981) Industrial and Environmental Xenobiotics. Springer, Berlin Heidelberg New York
Gut I, Nerudova J, Kopecky J, Holecek V (1975) Acrylonitrile biotransformation in rats, mice, and Chinese hamsters as influenced by the route of administration and by phnobarbital, SKF 525A, cysteine, dimercaprol, or thiosulfate. Arch Toxicol 33: 151–161
Hashimoto K, Kanai R (1965) Studies on the toxicology of Acrylonitrile; Metabolism, Mode of action and therapy. Ind Health 3: 30–45
Knight RH, Young L (1958) Biochemical studies of toxic agents. II. The occurrence of premercapturic acids. Biochem J 70: 111–119
Kopecky J, Gut I, Nerudova J, Zachardova D, Holecek V (1980) Two routes of acrylonitrile metabolism. J Hyg Epidem Microbiol 24; 3: 356–362
Langvard PW, Putzig CL, Braun WH, Young JD (1980) Identification of the major urinary metabolites of acrylonitrile in the rat. J Toxicol Environ Health 6: 273–282
Lin YY, Ahmed AE (1979) Analysis of the urinary metabolites of the carcinogen Acrylonitrile. Extended Abstr Annu Meeting, Am Soc Mass Spectro, p 613
Maltoni C, Ciliberti A, Dimaio V (1977) Carcinogenicity bioassays of rats of Acrylonitrile administered by inhalation and by ingestion. La Medicinadd Lavoro 68: 401–411
Murray FJ, Schwetz BA, Nitschke KD, Norris JM, Gehring PJ (1978) Teratogenicity of Acrylonitrile given to rats by gavage, or by inhalation. Fed Cosmet Toxicol 16: 547
O'berge MT (1980) Epidemiologic studies of workers exposed to Acrylonitrile. J Occupal Med 22(4): 245–252
Quast JF, Enriquez RM, Wade CE, Humiston CE, Schwetz BA (1978) Toxicity of drinking water containing Acrylonitrile in rats. Fed Reg 43: 2589
Sasame HA, Boyd MR (1978) Paradoxical effects of cobaltous chloride and salts of other divalenl melals on tissue levels of reduced glulathione and microsomal mixed-function oxidase components. J Pharmacol Exp Ther 205(3): 718–724
Szabo S, Bailey KA, Boor PJ, Jaeger RJ (1977) Acrylonitrile and tissue glutathione: Differential effect of acute and chronic interactions. Biochem Biophys Res Commun 79: 32–37
Toennies G, Kolb JJ (1951) Techniques and reagent for paper chromatography. Anal Chem 23: 823–826
Vainio H, Makinen A (1979) Styrene and acrylonitrile induced depression of hepatic nonprotein sulfhydryl content in various rodent species. Res Commun Chem Pathol Pharmacol 17: 115–124
Van Bladern PJ, Delbressine LPC, Hoogetrep JJ, Beaumont AH, Breimer DD, Seutter-Berlage F, Gen AV (1981) Formation of mercapturic acids from acrylonitrile, crotonitrile and cinnamonitrile by direct conjugation and via an intermediate oxidation process. Drug Metab Dispos 9: 246–249
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Ghanayem, B.I., Ahmed, A.E. In vivo biotransformation and biliary excretion of 1-14C-acrylonitrile in rats. Arch Toxicol 50, 175–185 (1982). https://doi.org/10.1007/BF00373400
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DOI: https://doi.org/10.1007/BF00373400