Archives of Toxicology

, Volume 64, Issue 5, pp 365–369 | Cite as

Pulmonary toxicity of inhaled styrene in acetone-, phenobarbital- and 3-methylcholanthrene-treated rats

  • E. Elovaara
  • H. Vainio
  • A. Aitio
Original Investigations

Abstract

Pulmonary changes in glutathione (GSH) indicated by the concentration of non-protein sulphydryls showed a decrease of 43% in rats exposed for 5 h per day three times to 500 cm3/m3 (2100 mg/m3) styrene vapour. In these rats, only a marginal decrease was observed in the pulmonary cytochrome P450 oxidative metabolism. Following a single 24-h inhalation exposure to 500 cm3/m3 styrene, the decreases in GSH were 66% in lung but only 16% in liver. On the other hand, a multifold increase in the disposition of thioether compounds was found in urine. Pulmonary cytochrome P450-dependent metabolism was decreased, shown by low residual activities of 7-ethoxyresorufin (<20%), 7-ethoxycoumarin (53%) and 7-pentoxyresorufin O-dealkylases (76%). Epoxide hydrolase and GSH S-transferase enzyme activities which catalyze styrene detoxification were not decreased. Styrene exposure (24 h) of acetone-, phénobarbitalor 3-methylcholanthrene-pretreated rats resulted in pulmonary effects different from each other and from those of styrene alone. Acetone potentiated the lung effect and elevated 1.5-fold urine thioether output. Inducer pretreatment seemed to be a factor aggravating styrene toxicity; in effect this was clearest in acetone-induced rats. In general, GSH depletion accompanied by inhibition of cytochrome P450-dependent oxidative drug metabolism were the earliest biochemical lesions manifested in styrene-exposed lung.

Key words

Styrene inhalation Phenobarbital Methylcholanthrene Acetone Microsomal drug-metabolizing enzymes Glutathione Thioethers Lung Liver Rat 

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Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • E. Elovaara
    • 1
  • H. Vainio
    • 1
  • A. Aitio
    • 1
  1. 1.Department of Industrial Hygiene and ToxicologyInstitute of Occupational HealthHelsinkiFinland

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