Exposure of rabbits to methylchloroform. Vestibular disturbances correlated to blood and cerebrospinal fluid levels

  • B. Larsby
  • R. Tham
  • L. M. Ödkvist
  • B. Norlander
  • D. Hydén
  • G. Aschan
  • A. Rubin


A previously described experimental model for studying the effects on the central nervous system of rabbits, specifically the vestibular apparatus, has been applied to methylchloroform. To achieve a steady concentration the solvent was infused as a lipid emulsion. The blood and cerebrospinal fluid kinetics have been studied. The arterial blood level seems to be closely correlated to the concentration in the central nervous tissue. Vestibular function has been studied by recording the involuntary eye movements — nystagmus — which are elicited via central vestibulo-oculomotor connections. At blood levels of methylchloroform above 75 ppm a so called “positional nystagmus”, indicated vestibular disturbances, is demonstrated. The relationship between the present findings in rabbits and the reaction and blood concentrations in people exposed to industrial solvents, are discussed.

Key words

Gas chromatography Industrial solvents Methylchloroform Vestibular disturbances 


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  1. 1.
    American Conference of Governmental Industrial Hygienists. Threshold limit values for chemical substances and physical agents in the workroom environment with intended changes for 1973Google Scholar
  2. 2.
    Aschan, G.: Different types of alcohol nystagmus. Acta Otolaryngol. Suppl 140, 69–78 (1958)Google Scholar
  3. 3.
    Aschan, G.: Studies on the ascending vestibuloocular reflex arc. Wenner-Gren Symposium No. 15, Oxford, New York: Pergamon Press (1970)Google Scholar
  4. 4.
    Aschan, G., Bergstedt, M.: Balanssinnesfunktion vid alkoholintoxikation. Ann. Acad. Regiae Scient, Upsaliensis, 1, 36–52 (1957)Google Scholar
  5. 5.
    Aschan, G., Bergstedt, M.: Positional alcoholic nystagmus (PAN) in man following rapeated alcohol doses. Acta Otolaryngol. Suppl. 330, 15–29 (1975)Google Scholar
  6. 6.
    Aschan, G., Bergstedt, M., Goldberg, L., Laurell, L.: Positional nystagmus in man during and after alcohol intoxication. Quart. J. Stud. Alcohol 17, 381–405 (1956)Google Scholar
  7. 7.
    Aschan, G., Bergstedt, M., Goldberg, L.: Positional alcohol nystagmus in patients with unilateral and bilateral labyrinthine destructions. Confin. neurol. 24, 80–102 (1964a)Google Scholar
  8. 8.
    Aschan, G., Ekvall, L., Grant, G.: Nystagmus following stimulation in the central vestibular pathways using permanently implanted electrodes. Acta Otolaryngol. Suppl. 192, 63–77 (1964)Google Scholar
  9. 9.
    Aschan, G., Bunnfors, I., Hydên, D., Larsby, B., Ödkvist, L.M., Tham, R.: Xylene exposure. Electronystagmographic and gaschromatographic studies in rabbits. Acta Otolaryngol. 84, 370–376 (1977)Google Scholar
  10. 10.
    Åstrand, I.: Uptake of solvents in the blood and tissues of man. A review. Scand. j. work environ. & health 1, 199–218 (1975)Google Scholar
  11. 11.
    Åstrand, I., Kilbom, A., Wahlberg, I., Övrum, P.: Methylchloroform exposure. I. Concentration in alveolar air and blood at rest and during exposure. Work-environs health 10, 68–91 (1973)Google Scholar
  12. 12.
    Axelsson, O., Hane, M., Hogstedt, C.: Neuropsychiatric ill-health in workers exposed to solvents — a case control study. Sv. Läkartidningen 73, 322–325 (1976)Google Scholar
  13. 13.
    Brodie, B.: Kinetics of absorption, distribution, excretion and metabolism of drugs. In Animal and clinical pharmacologic techniques in drug evaluation. Ed. Nodine, J. and Siegler, P. Vol. I, p. 69–88, Year Bk. 1967Google Scholar
  14. 14.
    Deutsche Forschungsgemeinschaft: MSK-Went; 1, 1, 1-Trichloroäthan; Weinheim: Verlag Chemie 1973Google Scholar
  15. 15.
    Gamberale, F., Hultengren, M.: Toluene exposure. II. Phychophysiological function. Workenviron.-health 9, 131–139 (1972)Google Scholar
  16. 16.
    Gamberale, G., Hultengren, M. Methylchloroform exposure. I. Psychophysiological functions. Work-environ.-health 10, 82–92 (1973)Google Scholar
  17. 17.
    Goldstein, A., Aranow, L., Kalman, S.: Principles of drug action. The basis of pharmacology. New York, London: John Wiley 1974Google Scholar
  18. 18.
    Japanese Association of Industrial Health: Recommended threshold limit values for 1973. Jap. J. industrial Health (Sangyo Igako) 15, 280–286 (1973)Google Scholar
  19. 19.
    Larsby, B., Ödkvist, L.M., Hydén, D., Liedrgren, S.R.C.: Disturbances of the vestibular system by toxic agents. Acta Phys. Scand. Suppl. 440, (1976)Google Scholar
  20. 20.
    Papper, E.M., Kitz, R.J.: Uptake and distribution of anasthetic agents. New York, Toronto, London: McGraw-Hill Book 1963Google Scholar
  21. 21.
    Report of the Swedish National Board of Occupational Safety and Health: Threshold limits in the workroom environment 1974Google Scholar
  22. 22.
    Salvini, M., Binaschi, S., Riva, M.: Evaluation of the psychophysiological functions in humans expsosed to the ‘Threshold Limit Value’ of 1, 1, 1-trichloroethane. Brit. J. industr. Med 28, 286–292 (1971)Google Scholar
  23. 23.
    Seppäläinen, A.M.: Application of neurophysiological methods in occupational medicine. Scand. j. work environ. & health 1, 1–14 (1975)Google Scholar
  24. 24.
    Stewart, R.D., Guy, H.H., Schaffer, A.W., Erley, D.S., Rowe, V.K.: Experimental human exposure to methylchloroform vapor. Arch. environm. hlth 19, 467–472 (1969)Google Scholar
  25. 25.
    Stewart, R.D., Andrews, J.T.: Acute intoxication with methylchloroform. JAMA (March 14) 195, 120–122 (1966)Google Scholar
  26. 26.
    Torkelson, T.R., Qyen, F., McCollister, D.D., Rowe, V.K.: Toxicity of 1, 1, 1-trichloroethane as determined on laboratory animals an human subjects. Amer. industr. hyg. Ass. J. 19, 353–362 (1958)Google Scholar

Copyright information

© Springer-Verlag 1978

Authors and Affiliations

  • B. Larsby
    • 1
  • R. Tham
    • 1
  • L. M. Ödkvist
    • 1
  • B. Norlander
    • 1
  • D. Hydén
    • 1
  • G. Aschan
    • 1
  • A. Rubin
    • 1
  1. 1.Department of Otolaryngology and Department of Clinical Pharmacology, Regional and University HospitalLinköping UniversityLinköpingSweden

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