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Species-Specific Inhalation Pharmacokinetics of 2-Nitropropane, Methyl Ethyl Ketone, and n-Hexane

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Biologically Based Methods for Cancer Risk Assessment

Abstract

2-Nitropropane (2-NP), methyl ethyl ketone (MEK), and n-hexane (HEX) are used in large quantities for industrial processes. They are components of solvent mixtures and are present as thinners in commercial products like glues, paints, and laquers. Because of their high volatility persons are mainly exposed via inhalation of the vapors.

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References

  • Abdel-Rahman, K. S., Hetland, L. B., and Couri, D., 1976, Toxicity and metabolism of methyl n-butyl ketone, Am. Ind. Hva. Assoc. J. 3:95

    Article  Google Scholar 

  • Altenkirch, H., Mager, J., Stoltenburg, G., and Helmbrecht, J., 1977, Toxic polyneuropathies after sniffing a glue thinner, J. Neurol. 214:137

    Article  PubMed  CAS  Google Scholar 

  • Altenkirch, H., Stoltenburg, G., and Wagner, H. M., 1978, Experimental studies on hydrocarbon neuropathies induced by methyl ethyl ketone (MER), J. Neurol. 219:159

    Article  PubMed  CAS  Google Scholar 

  • Altenkirch, H., Wagner, H.M., Stoltenburg, G., and Spencer, P.S., 1982

    Google Scholar 

  • Nervous system responses of rats to subchronic inhalation of n-hexane and n-hexane + methyl ethyl ketone mixtures, J. Neurol. Science 57:209

    Google Scholar 

  • Altman, P. L. and Dittmer, D. S., 1964, “Biology Data Book, vol. 3”, Federation of American Societies for Experimental Biology, Washington

    Google Scholar 

  • Andersen, M., E., 1981, A physiologically based toxicokinetic description of the metabolism of inhaled gases and vapors: Analysis at steady state, Toxicol. Appl. Pharmacol. 60: 509

    Article  CAS  Google Scholar 

  • Andrae, U., Homfeldt, H., Vogl, L., Lichtmannegger, J., and Summer, K. H., 1988, 2-Nitropropane induces DNA repair synthesis in rat hepatocytes in vitro and in vivo, Carcinoaenesis 9: 811

    Article  CAS  Google Scholar 

  • Anthony, D. C., Boekelheide, K., Anderson, C.W., and Graham, D. G., 1983, The effect of 3,4-dimethyl substitution on the neurotoxicity of 2,5-hexanedione. II. Dimethyl substitution accelerates pyrrole formation and protein crosslinking, Toxicol. Appl. Pharmacol. 71:372

    Article  PubMed  CAS  Google Scholar 

  • Baker, T. S. and Rickert, D. E., 1981, Dose-dependent uptake, distribution, and elimination of inhaled n-hexane in the Fischer-344 rat, Toxicol. Appl. Pharmacol. 61:414

    Article  PubMed  CAS  Google Scholar 

  • Böhlen, P., Schlunegger, U. P., and Läuppi, E., 1973, Uptake and distribution of hexane in rat tissues, Toxicol. Anal. Pharmacol. 25:242

    Google Scholar 

  • Bolt, H, M., Filser, J. G., and Störmer, F., 1984, Inhalation pharmacokinetics based on gas uptake studies V. Comparative pharmacokinetics of ethylene and 1,3-butadiene in rats, Arch. Toxicol. 55: 213

    CAS  Google Scholar 

  • Boxenbaum, H., 1980, Interspecies variations in liver weight, hepatic blood flow, and antipyrine intrinsic clearance: extrapolation of data to benzodiazopines and phenytoin, J. Pharmocokinet. Biopharmac. 8:165

    Article  CAS  Google Scholar 

  • Brugnone, F., Perbellini, L., Grigolini, L., and Apostoli, A., 1978

    Google Scholar 

  • Solvent exposure in a shoe factory. I. n-Hexane and acetone concentration in alveolar and environmental air and in blood, Int. Arch. Occup. Environ. Health 40:241

    Google Scholar 

  • Couri, D., and Milks, M., 1982, Toxicity and metabolism of the neurotoxic hexacarbons n-hexane, 2-hexanone, and 2,5-hexanedione, Ann. Rev. Pharmacol. 22:145

    Article  CAS  Google Scholar 

  • Dahl, A. R., Damon, E. G., Mauderly, J. L., Rothenberg, S. J., Seiler, F. A., and McClellan, R. O 1988, Uptake of 19 hydrocarbon vapors inhaled by F344 rats, Fundament. Appl. Toxicol. 10: 269

    Google Scholar 

  • DeCaprio, A. P., Strominger, N. L., and Weber, P., 1983, Neurotoxicity and protein binding of 2,5-hexanedione in the hen, Toxicol. Anal. Pharmacol. 68:297

    CAS  Google Scholar 

  • DeCaprio, A. P., and O’Neill, E. A., 1985, Alterations in rat axonal cytoskeletal proteins induced by in vitro and in vivo 2,5-hexanedione exposure, Toxicol. Anal. Pharmacol. 78:235

    CAS  Google Scholar 

  • DeCaprio, A. P., Briggs, R. G., Jackoswki, S. J., Kim, J. C. S., 1988, Comparative neurotoxicity and pyrrole-forming potential of 2,5-hexanedione in the rat, Toxicol. App1. Pharmacol. 92:75

    Article  CAS  Google Scholar 

  • Deutsche Forschungsgemeinschaft, 1976, 2-Butanon, in: “Toxikologischarbeitsmedizinische Begründung von MAK-Werten,” D. Henschler, ed., VCH, Weinheim

    Google Scholar 

  • Deutsche Forschungsgemeinschaft, 1982, n-Hexan, in: “Toxikologischarbeitsmedizinische Begründung von MAK-Werten”, D. Henschler, ed., VCH, Weinheim

    Google Scholar 

  • Dietz, F. K., and Traiger, G. J., 1979, Potentiation of CC14 hepatotoxicity in rats by a metabolite of 2-butanone: 2,3-butanediol, Toxicol. 14: 209

    CAS  Google Scholar 

  • Dietz, F. K., Rodriguez-Giaxola, M., Traiger, G. J., Stella, V. J., and Himmelstein, K. J., 1981, Pharmacokinetics of 2-butanol and its metabolites in the rat, J. Pharmacokin. Biopharm. 9:553

    Article  CAS  Google Scholar 

  • DiVicenzo, G. D., Kaplan, C. J., and Dedinas, J., 1976, Characterization of the metabolites of methyl n-butyl ketone, methyl isobutyl ketone, and methyl ethyl ketone in guinea pig serum and their clearance, Toxicol. ADpl. Pharmacol. 36:511

    Google Scholar 

  • Documenta Geigy, 1973, “Wissenschaftliche Tabellen”, 7. ed., Ciba-Geigy, Basel

    Google Scholar 

  • Duckett, S., Williams, N., and Francis, S., 1974, Peripheral neuropathy associated with inhalation of methyl n-butyl ketone, Experientia 30: 1283

    CAS  Google Scholar 

  • Fedtke, N. and Bolt, H. M., 1987, The relevance of 4,5-dihydroxy-2hexanone in the excretion kinetics of n-hexane metabolites in rat and man, Arch. Toxicol. 61:131

    Google Scholar 

  • Filser, J. G. and Bolt, H. M., 1979, Pharmacokinetics of halogenated ethylenes in rats, Arch. Toxicol. 42,123

    Google Scholar 

  • Filser, J. G. and Bolt, H. M., 1981, Inhalation kinetics based on gas uptake studies I. Improvement of kinetic models, Arch. Toxicol. 47:279

    Google Scholar 

  • Filser, J. G. and Bolt, H. M., 1983, Inhalation pharmacokinetics based on gas uptake studies IV. The endogenous production of volatile compounds, Arch. Toxicol. 52:123

    Google Scholar 

  • Filser, J. G., and Bolt, H. M., 1984, Inhalation pharmacokinetics based on gas uptake studies VI. Comparative evaluation of ethylene oxide and butadiene monoxide as exhaled reactive metabolites of ethylene and 1,3-butadiene in rats, Arch. Toxicol. 55:219

    Google Scholar 

  • Filser, J. G., Heilmaier, H. E., Summer, K. H., and Greim, H., 1987a, Spektralphotometrischer Test zur Bestimmung der 2,5-Hexandionbelastung aus dem Urin von Ratten, in: “Bericht Ober die 27. Jahrestagung der Deutschen Gesellschaft für Arbeitsmedizin e.V., Band 1”, K. Norpoth, ed., Gentner Verlag, Stuttgart

    Google Scholar 

  • Filser, J. G., Peter, H., Bolt, H. M., and Fedtke, N., 1987b, Pharmacokinetics of the neurotoxin n-hexane in rat and man, Arch. Toxicol. 60: 77

    Article  PubMed  CAS  Google Scholar 

  • Frommer, U., Ullrich, V., and Orrenius, S., 1974, Influence of inducers and inhibitors on the hydroxylation pattern of n-hexane in rat liver microsomes, FEBS Letters 41: 14

    CAS  Google Scholar 

  • Griffin, T. B., Coulston, F., and Stein, A. A., 1980, Chronic inhalation exposure of rats to vapors of 2-nitropropane at 25 ppm, Ecotoxicol. Environ. Safety 4:267

    Google Scholar 

  • Guyton, A. C., 1947, Respiratory volumes of laboratory animals, Am. J. Phvsiol. 150: 70

    CAS  Google Scholar 

  • Hallier, E., Filser, J. G., and Bolt, H. M., 1981, Inhalation pharmacokinetics based on gas uptake studies II. Pharmacokinetics of acetone in rats, Arch. Toxicol. 47:293

    Google Scholar 

  • Hilderbrand, R. L., and Andersen, M. E., 1981, In vivo kinetic constants for the metabolism of inhaled hydrocarbon toxicants as determined by gas uptake methods, Toxicoloaist 1: 86

    Google Scholar 

  • Krasavage, W. J., O’Donoghue, J. L., DiVincenzo, G. D., and Terhaar, C. J., 1980, The relative neurotoxicity of methyl n-butyl ketone, n-hexane and their metabolites, Toxicol. Appl. Pharmacol. 52:433

    Google Scholar 

  • Kreiling, R., Laib, R. J., Filser, J. G., and Bolt, H. M., 1986, Species differencesin butadiene metabolism between mice and rats evaluated by inhalation pharmacokinetics, Arch. Toxicol. 58:235

    Google Scholar 

  • Lewis, T. R., Ulrich, C. E., and Busey, W. M., 1979, Subchronic inhalation toxicity of nitromethane and 2-nitropropane, J. Environ. Pathol. Toxicol. 2:233

    Google Scholar 

  • Liira, J., Riihimäki, V., and Pfäffli, P., 1988, Kinetics of methyl ethyl ketone in man: absorption, distribution and elimination in inhalation exposure, Int. Arch. Environ. Health 60:195

    Google Scholar 

  • Lieser, K., 1983, “Tierexperimentelle Pharmakokinetik von 1,3-Butadien”, Inauguraldissertation im Fachbereich Medizin der Universität Mainz

    Google Scholar 

  • Miyasaka, M., Kumai, M., Koizumi, A., Watanabe, T., Kurasako, K., Sato, K., and Ikeda, M., 1982, Biological monitoring of occupational exposure to methyl ethyl ketone by means of urinalysis for methyl ethyl ketone itself, Int. Arch. Occup. Environ. Health 50:131

    Google Scholar 

  • Munies, R., and Wurster, D. E., 1965, Investigations of some factors influencing percutaneous absorption. III. Absorption of methyl ethyl ketone, J. Pharmacol. Sci. 54:1281

    Google Scholar 

  • Nolan, R. J., Unger, S. M., and Muller, C. J., 1982, Pharmacokinetics of inhaled [14C]-2-nitropropane in male Sprague-Dawley rats, Ecotoxicol. Environ. Safety 6:388

    Google Scholar 

  • Perbellini, L., DeGrandis, D., Semenzato, F., Rizzuto, N., and Simonati, A., 1978, An experimental study on the neurotoxicity of n-hexane metabolites: hexanol-1 and hexanol-2, Toxicol. Appl. Pharmacol. 46:241

    Google Scholar 

  • Perbellini, L., Brugnone, F., and Pavan, I., 1980, Identification of the metabolites of n-hexane, cyclohexane, and their isomers in men’s urine, Toxicol. Appl. Pharmacol. 53:220

    Google Scholar 

  • Perbellini, L., Brugnone, F., Mozzo, P., Cocheo, V., and Caretta, D., 1984, Methyl ethyl ketone exposure in industrial workers. Uptake and kinetics, Int. Arch. Occup. Environ. Health 54:73

    Google Scholar 

  • Perbellini, L., Brugnone, F., Caretta, C., and Maranelli, G., 1985, Partition coefficients of some industrial aliphatic hydrocarbons (C5–C7)in blood and human tissues, Br. J. Ind. Med. 42:162

    Google Scholar 

  • Perbellini, L., Mozzo, P., Brugnone, F., and Zedde, A., 1986, Physiologico-mathematical model for studying human exposure to organic solvents: kinetics of blood/tissue n-hexane concentrations and of 2,5-hexanedione in urine, Br. J. Ind. Med. 43:760

    Google Scholar 

  • Robertson, L. W., Regel, U., Filser, J. G., and Oesch, F., 1985, Absence of lipid peroxidation as determined by ethane exhalation in rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), Arch. Toxicol. 57:13

    Google Scholar 

  • Römmelt, H., and Dirnagl, K., 1977, Pulmonale Resorption von sechs Kohlenwasserstoffen in Abhängigkeit von der Konzentration in der Atemluft, Mùnch. med. Wschr. 119:367

    Google Scholar 

  • Saida, K., Mendell, J. R., and Weiss, H. S., 1976, Peripheral nerve changes induced by methyl n-butyl ketone and potentiation by methyl ethyl ketone, J. Neuropath. Exp. Neurol. 35:207

    Google Scholar 

  • Schaumburg, H. H., and Spencer, P. S., 1976, Degeneration in central and peripheral nervous systems produced by pure n-hexane: An experimental study, Brain, 99: 183

    Google Scholar 

  • Schwartz, L., 1898, Ober die Oxydation des Acetons and homologer Ketone der Fettsäurereihe, Arch. Exp. Pathol. Pharmakol. 40:168

    Google Scholar 

  • Siegers, P. C., Filser, J. G., and Bolt, H. M., 1978, Effect of ditiocarb on metabolism and covalent binding of carbon tetrachloride, Toxicol. Appl. Pharmacol. 46:709

    Google Scholar 

  • Spencer, P. S., Bischoff, M. C., and Schaumburg, H. H., 1978, On the specific molecular configuration of neurotoxic aliphatic hexacarbon compounds causing central-peripheral distal axonopathy, Toxicol. Appl. Pharmacol. 44:17

    Google Scholar 

  • Traiger, G. J., and Bruckner, J. V., 1976, The participation of 2butanone in 2-butanol-induced potentiation of carbon tetrachloride hepatotoxicity, J. Pharmacol. Exp. Ther. 196:493

    Google Scholar 

  • Veulemans, H., Van Vlem, E., Jansses, H., Masschelein, R., and Leplat, A., 1982, Experimental human exposure to n-hexane study of the respiratory uptake and of n-hexane: study of the respiratory uptake and elimination, and of n-hexane concentrations in peripheral venous blood, Ind. Arch. Occup. Environ. Health 49:251

    Google Scholar 

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Authors and Affiliations

  1. Institut für Toxikologie, GSF, Ingolstädter Landstr. 1, D-8042, Neuherberg, Germany

    Winfried Kessler, Barbara Denk & Johannes G. Filser

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  1. Winfried Kessler
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  2. Barbara Denk
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  3. Johannes G. Filser
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Editors and Affiliations

  1. Office of Risk Analysis, Oak Ridge National Laboratory, 37831-6109, Oak Ridge, Tennessee, USA

    Curtis C. Travis

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© 1989 Plenum Press, New York

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Kessler, W., Denk, B., Filser, J.G. (1989). Species-Specific Inhalation Pharmacokinetics of 2-Nitropropane, Methyl Ethyl Ketone, and n-Hexane. In: Travis, C.C. (eds) Biologically Based Methods for Cancer Risk Assessment. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5625-7_10

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  • DOI: https://doi.org/10.1007/978-1-4684-5625-7_10

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-5627-1

  • Online ISBN: 978-1-4684-5625-7

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