Skip to main content
Log in

Pharmacokinetics of the neurotoxin n-hexane in rat and man

  • Original Investigations
  • Metabolism of Xenobiotics
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

The pharmacokinetics of inhaled n-hexane in rat and man were compared. In the rat metabolism was saturable. Up to 300 ppm, the metabolic rate was directly proportional to the concentration in the atmosphere, reaching 47 μmol/(h· kg). Only 17% of n-hexane was exhaled unchanged. Above 300 ppm, the amount of n-hexane in the body rose with increasing atmospheric concentrations from 1.6 up to a limiting value of 9.6, which corresponded to the thermodynamic distribution coefficient of n-hexane between the organism and the atmosphere. Up to 3000 ppm, the rate of metabolism increased to 245 μmol/ (h· kg); only a slow further increase was found up to 7000 ppm (285μmol/(h· kg)).

In man the steady-state concentrations of n-hexane were about 1 ppm. The metabolic clearance was 1321/h, and n-hexane accumulated to a factor of 2.3 in the organism. The thermodynamic distribution coefficient was calculated to be 12. Twenty per cent of n-hexane in the body was exhaled unchanged.

At low concentrations the rate of metabolism of n-hexane is limited in both species by transport to the enzyme system. Under these conditions the rate of metabolism of n-hexane should not be influenced by xenobiotics which induce the n-hexane metabolizing enzyme system.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Anthony DC, Boekelheide K, Anderson CW, Graham DG (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 71:372–382

    Google Scholar 

  • Bolt HM, Filser JG, Buchter A (1981) Inhalation pharmacokinetics based on gas uptake studies. III. A pharmacokinetic assessment in man of “peak concentrations” of vinyl chloride. Arch Toxicol 48: 213–228

    Google Scholar 

  • Boxenbaum H (1980) Interspecies variation in liver weight, hepatic blood flow, and antipyrine intrinsic clearance: Extrapolation of data to benzodiazepines and phenytoin. J Pharmacokinet Biopharm 8: 165–176

    Google Scholar 

  • Buchter A, Bolt HM, Filser JG, Goergens HW, Laib RJ, Bolt W (1978) Pharmakokinetik und Karzinogenese von Vinylchlorid. Arbeitsmedizinische Risikobeurteilung. Verh Dtsch Ges Arbeitsmedizin (Gentner Verlag, Stuttgart) 18: 111–124

    Google Scholar 

  • Buchter A (1979) Erarbeitung einer speziellen arbeitsmedizinischen Überwachungsuntersuchung in Korrelation zur individuellen Vinylchlorid-Exposition. Forschungsbericht des Landes Nordrhein-Westfalen, Fachgruppe Medizin, Nr. 2813, Westdeutscher Verlag, Opladen

    Google Scholar 

  • Couri D, Milks M (1982) Toxicity and metabolism of the neurotoxic hexacarbons n-hexane, 2-hexanone, and 2,5-hexanedione. Ann Rev Pharmacol Toxicol 22: 145–166

    Google Scholar 

  • DeCaprio AP, Strominger NL, Weber P (1983) Neurotoxicity and protein binding of 2,5-hexanedione in the hen. Toxicol Appl Pharmacol 68: 297–307

    Google Scholar 

  • DGMK (1982) Evaluation of n-hexane toxicity in man and animals. Deutsche Gesellschaft für Mineralölwissenschaft und Kohlechemie e. V., DGMK-Project 174-2

  • Filser JG, Bolt HM (1981) Inhalation pharmacokinetics based on gas uptake studies. I. Improvement of kinetic models. Arch Toxicol 47: 279–292

    Google Scholar 

  • Filser JG, Bolt HM (1983) Inhalation pharmacokinetics based on gas uptake studies. IV. The endogenous production of volatile compounds. Arch Toxicol 52: 123–133

    Google Scholar 

  • Filser JG, Bolt HM, Muliawan H, Kappus H (1983) Quantitative evaluation of ethane and n-pentane as indicators of lipid peroxidation in vivo. Arch Toxicol 52: 135–147

    Google Scholar 

  • Nomiyama K, Nomiyama H (1974) Respiratory retention, uptake and excretion of organic solvents in man. Int Arch Arbeitsmed 32: 75–83

    Google Scholar 

  • Römmelt H, Dirnagl K (1977) Pulmonale Resorption von sechs Kohlenwasserstoffen in Abhängigkeit von der Konzentration in der Atemluft. Münch Med Wschr 119: 367–368

    Google Scholar 

  • Perbellini L, Brugnone F, Pavan I (1980) Identification of the metabolites of n-hexane, cyclohexane, and their isomeres in men's urine. Toxicol Appl Pharmacol 53: 220–229

    Google Scholar 

  • Schütz E, Caspers H, Speckmann E-J (1978) Physiologie. 15. Aufl., Urban & Schwarzenberg, München-Wien-Baltimore

    Google Scholar 

  • Siegers C-P, Filser JG, Bolt HM (1978) Effect of dithiocarb on metabolism and covalent binding of carbon tetrachloride. Toxicol Appl Pharmacol 46: 709–716

    Google Scholar 

  • Spencer PS, Schaumburg HH (1977) Ultrastructural studies of the dying-back process. IV. Differential vulnerability of PNS and CNS fibers in experimental central peripheral distal axonopathies. J Neuropathol Exp Neurol 36: 300–320

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Dedicated to Professor Dr. med. Herbert Remmer on the occasion of his 65th birthday

Rights and permissions

Reprints and permissions

About this article

Cite this article

Filser, J.G., Peter, H., Bolt, H.M. et al. Pharmacokinetics of the neurotoxin n-hexane in rat and man. Arch Toxicol 60, 77–80 (1987). https://doi.org/10.1007/BF00296952

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00296952

Key words

Navigation